Lacrimal implants and related methods

ABSTRACT

Lacrimal implants for treating diseases or disorders are disclosed. More particularly, lacrimal implants, methods of making such implants, and methods of treating ocular, respiration, inner ear or other diseases or disorders using such implants are disclosed.

CLAIM OF PRIORITY

This application is a Continuation application of U.S. Ser. No.13/598,201, which was filed 29 Aug. 2012 which is a divisionalapplication of U.S. patent application Ser. No. 12/231,989 (U.S. Pat.No. 8,333,726), filed 8 Sep. 2008, which claims the benefit of priorityunder 35 U.S.C. §119(e) to U.S. Provisional Patent Application Ser. No.60/970,696 filed on 7 Sep. 2007; U.S. Provisional Patent ApplicationSer. No. 60/970,720 filed on 7 Sep. 2007; U.S. Provisional PatentApplication Ser. No. 60/974,367 filed on 21 Sep. 2007; U.S. ProvisionalPatent Application Ser. No. 61/033,211 filed on 3 Mar. 2008; U.S.Provisional Patent Application Ser. No. 61/036,816 filed on 14 Mar.2008; U.S. Provisional Patent Application Ser. No. 61/049,360 filed on30 Apr. 2008; U.S. Provisional Patent Application Ser. No. 61/052,595filed on 12 May 2008; and U.S. Provisional Patent Application Ser. No.61/075,309 filed on 24 Jun. 2008, the specifications of all of which areherein incorporated by reference in their entireties.

TECHNICAL FIELD

This patent document pertains generally to ophthalmic devices, andparticularly to ocular implants. More particularly, but not by way oflimitation, this patent document pertains to lacrimal implants, methodsof making such implants, and methods of treating ocular, respiration,inner ear or other diseases or disorders (e.g., pulmonary orimmunological disorders) using such implants.

BACKGROUND

Dry eye, including keratoconjunctivitis sicca, is a common ocularcondition that can require therapy. Dry eye has been experienced by abroad demographic band, and is common in elderly individuals. A varietyof current treatment modalities target physiological conditions thatcontribute to dry eye, including augmentation of normal tear fluid,enhancement of tear film component production, and methods to enhancethe residence time of tears, such as blocking the tear flow from an eyeinto and through a lacrimal canaliculus.

Many current tear flow blockage techniques have drawbacks, includingbeing irreversible in nature. For instance, some tear flow blockagetechniques involve closing the canalicular canal by stitching thepunctal opening shut or by using electrical or laser cauterization toseal the punctal opening. Although such procedures can provide thedesired result of blocking tear flow to treat a dry eye, they areunfortunately not reversible without reconstructive surgery.

In addition to dry eye symptom relief, a variety of challenges facepatients and physicians in the area of ocular, respiration and inner eardisease or disorder management, including adequate drug or othertherapeutic agent delivery to the eyes, nasal passage or inner ear. Inocular management, for example, many current ocular drug deliverysystems require repetitive manual administration and are oftenineffective due to a lack of patient compliance or inadequate drugconcentrations reaching the eye.

In order to treat eye infection, inflammation of an eye, glaucoma andother ocular diseases or disorders, drugs or other therapeutic agentsare often required to be administered to the eye. A conventional methodof drug delivery is by topical drop application to the eye's surface.Topical eye drops, though effective, can be inefficient. As one example,when an eye drop is instilled in an eye, it often overfills theconjunctival sac (i.e., the pocket between the eye and the lids) causinga substantial portion of the drop to be lost due to overflow of the lidmargin and spillage onto the cheek. In addition, a large portion of thedrop remaining on the ocular surface can be washed away into and througha lacrimal canaliculus, thereby diluting the concentration of the drugbefore it can absorbingly treat the eye. Moreover, topically applieddrugs often have a peak ocular effect for about two hourspost-application, after which additional applications of the drugsshould be, but are often not, administered to maintain the desired drugtherapeutic benefit.

To compound ocular management difficulty, patients often do not usetheir eye drops as prescribed. This poor compliance can be due to, forexample, an initial stinging or burning sensation caused by the eye dropand experience by a patient. Instilling eye drops in one's own eye canbe difficult, in part because of the normal reflex to protect the eye.Therefore, one or more drops may miss the eye. Older patients may haveadditional problems instilling drops due to arthritis, unsteadiness, anddecreased vision. Pediatric and psychiatric populations posedifficulties as well.

In a field different from ocular management, control ofrespiration-related (e.g., allergies) and inner ear diseases ordisorders often requires repetitive manual digestion or other intake ofa medication (e.g., drugs or other therapeutic agents), and as such, canbe ineffective due to a lack of patient compliance or non-localized drugdelivery.

EXEMPLARY ASPECTS AND EMBODIMENTS OF THE INVENTION

The present inventors have recognized various promising techniques toincrease the residence time of tears on an eye and delivery of drug orother therapeutic agent to the eye, nasal passage, inner ear or othersystem. These techniques can include placing a removable, and optionallydrug releasing, lacrimal implant through a lacrimal punctum and into theassociated canaliculus. It is believed that by designing lacrimalimplants that utilize the features of the nasolacrimal drainage system,patient comfort and implant retention in the ocular anatomy can besatisfied. In this way, the present lacrimal implants can overcome someof the drawbacks associated with current dry eye relief, such as beingirreversible in nature, and ocular drug administration (e.g., manualdrop instillation or digestion), such as poor patient compliance, waste,untimely application, or non-localized delivery.

Further yet, the present inventors have recognized that a lacrimalimplant can benefit from one or more of: the ability to be easilyimplanted and removed without much biasing of the lacrimal punctum orassociated canaliculus, the ability to be securely retainable in thelacrimal canaliculus upon implantation, optionally without beingpre-sized to a particular lacrimal punctum or canaliculus, the abilityto permit tear fluid, drug or other agent to flow into the nasolacrimalsystem, and, when made and used as a drug delivery system, the abilityto allow for the sustained, localized release of one or more drugs orother therapeutic agents at a desired therapeutic level for an extendedperiod of time.

Lacrimal implants for treating diseases or disorders are disclosed. Moreparticularly, lacrimal implants, methods of making such implants, andmethods of treating ocular, respiration, inner ear, pulmonary orimmunological diseases or disorders using such implants are disclosed.

To better illustrate the subject matter described herein, a non-limitinglist of exemplary aspects and embodiments is provided here:

1. A lacrimal implant insertable into a lacrimal canaliculus,comprising: an implant body, including first and second portions, theimplant body extending from a proximal end of the first portion to adistal end of the second portion; the proximal end of the first portiondefining a longitudinal proximal axis and the distal end of the secondportion defining a longitudinal distal axis; the implant body configuredsuch that, when implanted in the lacrimal canaliculus, an angledintersection exists between the proximal axis and the distal axis forbiasing at least a portion of the implant body against at least aportion of the lacrimal canaliculus located at or more distal to acanalicular curvature; and wherein the second portion of the implantbody includes a longitudinal length having a magnitude less than fourtimes a longitudinal length of the first portion of the implant body.

2. The lacrimal implant according to aspect 1, wherein the implant bodyis configured such that an angled intersection exists between theproximal axis and the distal axis prior to being implanted in thelacrimal canaliculus.

3. The lacrimal implant according to any of aspects 1 or 2, wherein theimplant body is configured to partially or completely inhibit fluid flowinto and through the lacrimal canaliculus.

4. The lacrimal implant according to any of aspects 1-3, wherein adistal end of the first portion is integral with the second portion ator near a proximal end of the second portion.

5. The lacrimal implant according to any of aspects 1-4, wherein one orboth of the first portion or the second portion includes a fluidswellable retention element configured to expand.

6. The lacrimal implant according to aspect 5, wherein the secondportion includes the fluid swellable retention element, the fluidswellable retention element configured to expand laterally, relative tothe proximal axis of the first portion, when the implant body isimplanted.

7. The lacrimal implant according to any of aspects 5 or 6, wherein thefluid swellable retention element includes a portion configured toexpand laterally in a direction away from a lacrimal canaliculus ampullawhen the implant body is implanted.

8. The lacrimal implant according to any of aspects 5-7, wherein thefluid swellable retention element includes a portion configured toexpand laterally in a direction toward a lacrimal canaliculus ampullawhen the implant body is implanted.

9. The lacrimal implant according to any of aspects 1-8, wherein thesecond portion includes an expandable retention element comprising atleast one of a coil, a braid, a stent, a mesh tube, a suture, athermoset polymer, a thermoplastic, a heat activatable material, or ashape memory material, the expandable retention element configured toexpand laterally, to form the angled intersection, when the implant bodyis implanted.

10. The lacrimal implant according to any of aspects 1-9, comprising anexpandable retention element disposed around a portion of the secondportion, the expandable retention element configured to bias the secondportion away from a wall of the lacrimal canaliculus upon expansion.

11. The lacrimal implant according to any of aspects 1-10, wherein thesecond portion includes an arm member movable between a firstconfiguration and a second configuration; the arm member, in the firstconfiguration, disposable along the implant body for insertion into thelacrimal canaliculus and, in the second configuration, laterallyextendable from one side of the implant body.

12. The lacrimal implant according to any of aspects 1-11, wherein thesecond portion includes an integral dilator, the integral dilatorgenerally narrowing from a location near a proximal end of the secondportion to the distal end of the second portion to facilitateimplantation of the implant body into the lacrimal canaliculus.

13. The lacrimal implant according to aspect 12, wherein a diameter ofan integral dilator tip is between about 0.2 millimeters and about 0.5millimeters.

14. The lacrimal implant according to any of aspects 12 or 13, whereinan outer surface slope of the integral dilator, as measured from thelocation near the proximal end of the second portion to the distal endof the second portion, is between about 1 degree and about 10 degreeswith respect to the distal axis.

15. The lacrimal implant according to any of aspects 1-14, wherein thesecond portion includes at least one undulation.

16. The lacrimal implant according to any of aspects 1-15, wherein atleast one of the first portion or the second portion comprises at leastone intermediately-disposed annular, semi-annular, column-like, orbarrel-like projection, the intermediately-disposed projection having across-sectional size greater than an adjacent implant body portion.

17. The lacrimal implant according to any of aspects 1-16, comprising agraspable projection extending at least partially from the proximal endof the first portion, the graspable projection configured to seatagainst or near a lacrimal punctum when the implant body is implanted.

18. The lacrimal implant according to aspect 17, wherein the secondportion includes an element extending or expanding laterally into alacrimal canaliculus ampulla when the implant body is implanted.

19. The lacrimal implant according to any of aspects 17 or 18, whereinthe graspable projection extends laterally from the proximal end of thefirst portion, in a direction that is parallel to or away from an eye,when the implant body is implanted.

20. The lacrimal implant according to any of aspects 1-19, wherein theimplanted angled intersection of the proximal axis and the distal axisis at least about 45 degrees.

21. The lacrimal implant according to any of aspects 1-20, comprising atherapeutic agent.

22. The lacrimal implant according to aspect 21, comprising at least onedrug insert including a drug core, the drug core comprising thetherapeutic agent.

23. The lacrimal implant according to aspect 22, wherein the drug corecomprises at least one exposed surface to deliver a sustained release.

24. A kit comprising the lacrimal implant according to any of aspects1-23, and an instruction for using the lacrimal implant to treat an eyedisease.

25. A kit comprising the lacrimal implant according to any of aspects1-23, and an instruction for using the lacrimal implant to treat arespiration-related disorder.

26. A kit comprising the lacrimal implant according to any of aspects1-23, and an instruction for using the lacrimal implant to treat aninner ear disorder.

27. A lacrimal implant for insertion into a lacrimal canaliculus,comprising: an implant body non-linearly extending from a proximal endportion positionable within a vertical section of the lacrimalcanaliculus to a distal end portion positionable within a horizontalsection of the lacrimal canaliculus and having an intermediate portiontherebetween; the intermediate portion partially extending in a firstdirection toward the proximal end portion and partially extending in asecond direction toward the distal end portion such that, when implantedin the lacrimal canaliculus, the implant body directionally biaseslaterally against at least a portion of the lacrimal canaliculus locatedat or more distal to a canalicular curvature; and wherein the implantbody inhibits fluid flow into and through the lacrimal canaliculus.

28. The lacrimal implant according to aspect 27, wherein a longitudinallength of the implant body positionable within the vertical section ofthe lacrimal canaliculus is less than four times a longitudinal lengthof the implant body positionable within the horizontal section of thelacrimal canaliculus.

29. The lacrimal implant according to any of aspects 27 or 28, whereinthe first direction extension of the intermediate portion is at an anglebetween about 45 degrees and about 135 degrees relative to the seconddirection extension of the intermediate portion.

30. The lacrimal implant according to any of aspects 27-29, wherein theintermediate portion partially extends in a third direction,substantially opposite the second direction, toward a lacrimalcanaliculus ampulla when the implant body is implanted.

31. The lacrimal implant according to any of aspects 27-30, wherein thesecond direction extension includes a longitudinal dilator having agenerally concave shape relative to the first direction extension; andwherein a radius of the generally concave shape is less than the radiusof the canaliculus curvature.

32. The lacrimal implant according to any of aspects 27-31, wherein thesecond direction extension includes a longitudinal dilator having agenerally convex shape relative to the first direction extension.

33. The lacrimal implant according to any of aspects 27-32, wherein thesecond direction extension includes a longitudinal dilator having anaxis substantially perpendicular to an axis of the first directionextension.

34. The lacrimal implant according to any of aspects 27-33, wherein atleast one of the proximal end portion or the distal end portioncomprises at least one intermediately-disposed annular, semi-annular,column-like, or barrel-like projection, the intermediately-disposedprojection having a cross-sectional size greater than an adjacentimplant body portion.

35. The lacrimal implant according to any of aspects 27-34, comprising agraspable projection, the graspable projection extending laterally fromthe proximal end portion.

36. The lacrimal implant according to any of aspects 27-35, comprising afluid swellable material disposed on an outer surface portion of theimplant body, the fluid swellable material configured to expand an outersurface diameter portion of the implant body when implanted.

37. The lacrimal implant according to any of aspects 27-36, comprisingat least one of a first drug insert disposed in the proximal end portionor a second drug insert disposed in the distal end portion, one or bothof the first or second drug inserts inhibiting fluid flow through theimplant body and including at least one exposed surface configured todeliver a sustained release.

38. The lacrimal implant according to aspect 37, comprising a cavity inthe proximal end portion, the cavity configured to house the first druginsert in the form of a drug core, the drug core including a first agentconfigured to treat an eye.

39. The lacrimal implant according to any of aspects 37 or 38,comprising a cavity in the distal end portion, the cavity configured tohouse the second drug insert in the form of a drug core, the drug coreincluding a second agent configured to be received by a nasal passage.

40. A method of manufacturing a lacrimal implant insertable into alacrimal canaliculus, the method comprising: forming an implant bodyextending from a proximal end of a first body portion to a distal end ofa second body portion, including extending the second body portion to alongitudinal length which is less than four times a longitudinal lengthof the first body portion; and configuring the proximal end and thedistal end to respectively define, when implanted in the lacrimalcanaliculus, a longitudinal proximal axis and a longitudinal distal axisthat intersect at an angle such that the implant body is configured todirectionally bias laterally against at least a portion of the lacrimalcanaliculus located at or more distal to a canaliculus curvature.

41. The method according to aspect 40, wherein forming one or both ofthe first body portion or the second body portion includes forming atleast one intermediately-disposed annular, semi-annular, column-like, orbarrel-like projection, the intermediately-disposed projection having across-sectional size greater than an adjacent implant body portion.

42. The method according to any of aspects 40 or 41, wherein forming thesecond body portion includes forming a dilator generally narrowing froma location near a proximal end of the second body portion to the distalend of the second body portion.

43. The method according to any of aspects 40-42, wherein forming thedilator includes forming an outer surface slope of the implant body, asmeasured from the location near the proximal end of the second bodyportion to the distal end of the second body portion, between about 1degree and about 10 degrees with respect to the longitudinal distalaxis.

44. The method according to any of aspects 40-43, wherein forming thesecond potion includes disposing a fluid swellable retention elementnear a distal end of the first body portion, including disposing thefluid swellable retention element such that a lateral expansion thereof,relative to the proximal axis, is configured to bias against at least aportion of the lacrimal canaliculus or a lacrimal canaliculus ampullaanatomy when the implant body is implanted.

45. The method according to any of aspects 40-44, comprising coating anouter surface portion of the implant body with a fluid swellablematerial.

46. The method according to any of aspects 40-45, comprising disposingat least one of a first drug insert in the first body portion or asecond drug insert in the second body portion, including positioning atleast one of an exposed surface of the first drug insert adjacent to theproximal end or an exposed surface of the second drug insert adjacent tothe distal end to provide a sustained release of a first agent or asecond agent, respectively.

47. A method of treating a patient having at least one of an eyedisorder, a respiration-related disorder, a pulmonary disorder, animmunological disorder or an inner ear disorder, the method comprising:inserting a lacrimal implant into at least one lacrimal canaliculus ofthe patient, the lacrimal implant comprising, an implant body, includingfirst and second portions, the implant body extending from a proximalend of the first portion to a distal end of the second portion, theproximal end defining a longitudinal proximal axis and the distal axisdefining a longitudinal distal axis; the implant body configured suchthat, when implanted in a lacrimal canaliculus, an angled intersectionexists between the proximal axis and the distal axis for biasing atleast a portion of the implant body against at least a portion of thelacrimal canaliculus located at or more distal to a canalicularcurvature; and at least one of a first drug insert disposed in the firstportion or a second drug insert disposed in the second portion, thefirst and second drug inserts configured to respectively provide asustained release of a first agent or a second agent.

48. The method according to aspect 47, wherein inserting the lacrimalimplant includes concurrently dilating the lacrimal canaliculus, usingan integral dilator of the implant body, as the distal end of the secondportion is moved into the lacrimal canaliculus.

49. The method according to any of aspects 47 or 48, comprising removingthe inserted implant body from the lacrimal canaliculus.

50. The method according to any of aspects 47-49, comprising replacingthe lacrimal implant that has been inserted with a second lacrimalimplant including at least one of the same first or second agentfollowing an interval of time.

These and other embodiments, advantages, and aspects of the presentlacrimal implants and methods will be set forth in part in followingDetailed Description. This Summary is intended to provide an overview ofsubject matter of the present patent application. It is not intended toprovide an exclusive or exhaustive explanation of the present invention.The Detailed Description is included to provide further informationabout the present patent application.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, like numerals can be used to describe similarcomponents throughout the several views. Like numerals having differentletter suffixes can be used to represent different instances of similarcomponents. The drawings illustrate generally, by way of example, butnot by way of limitation, various embodiments discussed in the presentdocument.

FIGS. 1-2 illustrate examples of schematic views of anatomical tissuestructures associated with the eye, such tissue structures providing asuitable environment in which a lacrimal implant can be used.

FIG. 3A illustrates an example of an isometric view of a lacrimalimplant configured to be retained within a lacrimal punctum andassociated canalicular anatomy, the lacrimal implant including asubstantially perpendicular angled intersection between first and secondimplant body portions.

FIG. 3B illustrates an example of a cross-sectional view of a lacrimalimplant taken along a line parallel to a longitudinal axis of theimplant, such as along line 3B-3B, and a dilation of animplant-receiving anatomical tissue structure.

FIG. 4 illustrates an example of a side view of a lacrimal implantconfigured to be retained within a lacrimal punctum and associatedcanalicular anatomy, the lacrimal implant including an integral dilator.

FIG. 5 illustrates an example of a schematic view of a lacrimal implantretained within a lacrimal punctum and associated canalicular anatomy,the lacrimal implant including at least one drug insert.

FIG. 6A illustrates an example of an isometric view of a lacrimalimplant configured to be retained within a lacrimal punctum andassociated canalicular anatomy, the lacrimal implant including a portiondisposable within a lacrimal canaliculus ampulla.

FIG. 6B illustrates an example of a cross-sectional view of a lacrimalimplant taken along a line parallel to a longitudinal axis of theimplant, such as along line 6B-6B.

FIG. 7A illustrates an example of an isometric view of a lacrimalimplant configured to be retained within a lacrimal punctum andassociated canalicular anatomy, the lacrimal implant including anannular graspable projection.

FIG. 7B illustrates an example of a cross-sectional view of a lacrimalimplant taken along a line parallel to a longitudinal axis of theimplant, such as along line 7B-7B.

FIG. 8A illustrates an example of an isometric view of a lacrimalimplant configured to be retained within a lacrimal punctum andassociated canalicular anatomy, the lacrimal implant including a portiondisposable within a lacrimal canaliculus ampulla and including aninsertion-facilitating depression.

FIG. 8B illustrates an example of a cross-sectional view of a lacrimalimplant taken along a line parallel to a longitudinal axis of theimplant, such as along line 8B-8B.

FIG. 9 illustrates an example of side view of a lacrimal implantconfigured to be retained within a lacrimal punctum and associatedcanalicular anatomy, the lacrimal implant including aninsertion-facilitating depression.

FIG. 10A illustrates an example of an isometric view of a lacrimalimplant configured to be retained within a lacrimal punctum andassociated canalicular anatomy, the lacrimal implant including a portiondisposable within a lacrimal canaliculus ampulla.

FIG. 10B illustrates an example of a cross-sectional view of a lacrimalimplant taken along a line parallel to a longitudinal axis of theimplant, such as along line 10B-10B.

FIGS. 11-13 illustrate examples of a side view of various lacrimalimplants configured to be retained within a lacrimal punctum andassociated canalicular anatomy, each lacrimal implant including at leastone intermediately-disposed retainment projection.

FIGS. 14-17 illustrate examples of an isometric view of various lacrimalimplants configured to be retained within a lacrimal punctum andassociated canalicular anatomy, each lacrimal implant including at leastone intermediately-disposed retainment projection.

FIGS. 18-19 illustrate examples of a side view of lacrimal implantsconfigured to be retained within a lacrimal punctum and associatedcanalicular anatomy, each lacrimal implant including a non-perpendicularangled intersection between first and second implant body portions.

FIG. 20 illustrates an example of an isometric view of a lacrimalimplant configured to be retained within a lacrimal punctum andassociated canalicular anatomy, the lacrimal implant including one ormore material cutouts.

FIGS. 21A-22B illustrate examples of a side view of lacrimal implantsconfigured to be retained within a lacrimal punctum and associatedcanalicular anatomy, each lacrimal implant including one or morelaterally extendable arms.

FIGS. 23A-23B illustrate examples of a side view of a lacrimal implantconfigured to be retained within a lacrimal punctum and associatedcanalicular anatomy, the lacrimal implant including an expandableretention element disposed around a portion of the implant body.

FIG. 24 illustrates an example of a schematic view of a lacrimal implantretained within a lacrimal punctum and associated canalicular anatomy.

FIGS. 25A-25B illustrate examples of an isomeric view of lacrimalimplants configured to be retained within a lacrimal punctum andassociated canalicular anatomy, each lacrimal implant including animplant body portion having a generally concave shape.

FIG. 26 illustrates an example of an isometric view of a lacrimalimplant configured to be retained within a lacrimal punctum andassociated canalicular anatomy, the lacrimal implant including animplant body portion having a generally convex shape.

FIG. 27 illustrates an example of a side view of a lacrimal implantconfigured to be retained within a lacrimal punctum and associatedcanalicular anatomy, the lacrimal implant including an implant bodyportion having an undulating shape.

FIG. 28 illustrates an example of a side view of a lacrimal implantconfigured to be retained within a lacrimal punctum and associatedcanalicular anatomy, the lacrimal implant including at least oneintermediately-disposed retainment projection.

FIGS. 29-32 illustrate examples of a side view of various lacrimalimplants configured to be retained within a lacrimal punctum andassociated canalicular anatomy, each lacrimal implant including a fluidswellable retention element.

FIG. 33 illustrates an example of a side view of a lacrimal implantconfigured to be retained within a lacrimal punctum and associatedcanalicular anatomy, the lacrimal implant including an expandableretention element.

FIGS. 34A-34B illustrate examples of a schematic view of lacrimalimplants retained within a lacrimal punctum and associated canalicularanatomy, each lacrimal implant including an oriented graspableprojection.

FIGS. 35-38 illustrate examples of an isomeric view of various lacrimalimplant proximal end portions, each proximal end portion including agraspable projection or void.

FIGS. 39A-39B illustrate examples of an isomeric view of drug insertsand a removal-facilitating filament.

FIG. 40 illustrates an example of a method of manufacturing a lacrimalimplant configured to be retained within a lacrimal punctum andassociated canalicular anatomy.

DETAILED DESCRIPTION

In this patent document, lacrimal implants and related methods providingsecure, wedgable retention within a lacrimal punctum and associatedcanaliculus of an eye are described. The lacrimal implants can comprisean implant body configured for at least partial insertion through thelacrimal punctum and into the associated canaliculus. The implant bodycan include first and second portions, and can extend from a proximalend of the first portion defining a longitudinal proximal axis to adistal end of the second portion defining a longitudinal distal axis.The implant body can be configured such that, when implanted using anintegral dilator, an at least 45 degree angled intersection, forexample, exists between the proximal axis and the distal axis. In thisway, at least a portion of the implant body can be biased against atleast a portion of the lacrimal canaliculus located at or more distal toa canalicular curvature, thereby retaining an implanted position of thelacrimal implant using anatomical structures. In various examples, thelacrimal implant can further comprise a drug insert including a druginsert disposed in at least one of the first portion or the secondportion of the implant body, providing a sustained release of a drug orother therapeutic agent to one or more of an eye, nasal passage or innerear system.

FIGS. 1-2 illustrate examples of schematic views of anatomical tissuestructures associated with an eye 100. The anatomical tissue structuresshown are suitable for treatment using the various lacrimal implants andmethods discussed herein. As shown, the eye 100 is a spherical structureincluding a wall having three layers: an outer sclera 102, a middlechoroid layer 104 and an inner retina 106. The sclera 102 includes atough fibrous coating that protects the inner layers. It is mostly whiteexcept for the transparent area at the front, commonly known as thecornea 108, which allows light to enter the eye 100.

The choroid layer 104, situated inside the sclera 102, contains manyblood vessels and is modified at the front of the eye 100 as a pigmentediris 110. A biconvex lens 112 is situated just behind the pupil. Achamber 114 behind the lens 112 is filled with vitreous humour, agelatinous substance. Anterior and posterior chambers 116 are situatedbetween the cornea 108 and iris 110, respectively and filled withaqueous humour. At the back of the eye 100 is the light-detecting retina106.

The cornea 108 is an optically transparent tissue that conveys images tothe back of the eye 100. It includes avascular tissue to which nutrientsand oxygen are supplied via bathing with lacrimal fluid and aqueoushumour as well as from blood vessels that line the junction between thecornea 108 and sclera 102. The cornea 108 includes a pathway for thepermeation of drugs into the eye 100.

Turning to FIG. 2, other anatomical tissue structures associated withthe eye 100 including the lacrimal drainage system, which includes asecretory system 230, a distributive system and an excretory system, areshown. The secretory system 230 comprises secretors that are stimulatedby blinking and temperature change due to tear evaporation and reflexsecretors that have an efferent parasympathetic nerve supply and secretetears in response to physical or emotional stimulation. The distributivesystem includes the eyelids 202 and the tear meniscus around the lidedges of an open eye, which spread tears over the ocular surface byblinking, thus reducing dry areas from developing.

The excretory part of the lacrimal drainage system includes, in order offlow drainage, the lacrimal puncta, the lacrimal canaliculi, thelacrimal sac 204 and the lacrimal duct 206. From the lacrimal duct 206,tears and other flowable materials drain into a passage of thenasolacrimal system. The lacrimal canaliculi include an upper (superior)lacrimal canaliculus 208 and a lower (inferior) lacrimal canaliculus210, which respectively terminate in an upper 212 and lower 214 lacrimalpunctum. The upper 212 and lower 214 punctum are slightly elevated atthe medial end of a lid margin at the junction 216 of the ciliary andlacrimal portions near a conjunctival sac 218. The upper 212 and lower214 punctum are generally round or slightly ovoid openings surrounded bya connective ring of tissue. Each of puncta 212, 214 leads into avertical portion 220, 222 of their respective canaliculus before turningmore horizontal at a canaliculus curvature 250 to join one another atthe entrance of the lacrimal sac 204. The canaliculi 208, 210 aregenerally tubular in shape and lined by stratified squamous epitheliumsurrounded by elastic tissue, which permits them to be dilated. Asshown, a lacrimal canaliculus ampulla 252 exists near an outer edge ofeach canaliculus curvature 250.

FIG. 3A illustrates an example of a lacrimal implant 300 that can beinsertable through a lacrimal punctum 212, 214 and into the associatedcanaliculus 208, 210 (FIG. 2). The insertion of the lacrimal implant 300through the lacrimal punctum 212, 214 and into the associatedcanaliculus 208, 210 can allow for one or more of: inhibition orblockage of tear flow therethrough (e.g., to treat dry eyes) or thesustained delivery of a drug or other therapeutic agent to an eye (e.g.,to treat an infection, inflammation, glaucoma or other ocular disease ordisorder), a nasal passage (e.g., to treat a sinus or allergy disorder)or an inner ear system (e.g., to treat dizziness or a migraine).

As shown in this example, the lacrimal implant 300 can comprise animplant body 302 including first 304 and second 306 portions, and canextend from a proximal end 308 of the first portion 304 to a distal end310 of the second portion 306. In various examples, the proximal end 308can define a longitudinal proximal axis 312 and the distal end 310 candefine a longitudinal distal axis 314. The implant body 300 can beconfigured such that, when implanted within the lacrimal punctum andassociated canaliculus, an at least 45 degree angled intersection 316exists between the proximal axis 312 and the distal axis 314 for biasingat least a portion of the implant body 302 against at least a portion ofa lacrimal canaliculus 208, 210 (FIG. 2) located at or more distal to acanaliculus curvature 250 (FIG. 2). In some examples, the implant body302 can be configured such that the angled intersection 316 is betweenabout 45 degrees and about 135 degrees. In this example, the implantbody 302 is configured such that the angled intersection 316 is about 90degrees (i.e., the intersection 316 is about perpendicular). In variousexamples, a distal end 326 of the first portion 304 can be integral withthe second portion 306 at or near a proximal end 328 of the secondportion 306.

In certain examples, the implant body 302 can include angularly disposedcylindrical-like structures comprising one or both of a first cavity 318disposed near the proximal end 308 or a second cavity 320 disposed nearthe distal end 310. In this example, the first cavity 318 extends inwardfrom the proximal end 308 of the first portion 304, and the secondcavity 320 extends inward from the distal end 310 of the second portion306. A first drug-releasing or other agent-releasing insert (e.g., drugcore) 322 can be disposed in the first cavity 318 to provide a sustaineddrug or other therapeutic agent release to an eye, while a seconddrug-releasing or other agent-releasing insert (e.g., drug core) 324 canbe disposed in the second cavity 320 to provide a sustained drug orother therapeutic agent release to a nasal passage or inner ear system,for example. An implant body septum 330 can be positioned between thefirst cavity 318 and the second cavity 320, and can be used to inhibitor prevent communication of a material (e.g., agent) between the firstdrug insert 322 and the second drug insert 324. In some examples, theimplant body 302 is solid and does not include one or more cavities orother voids.

In some examples, the drug or other therapeutic agent release can occur,at least in part, via an exposed, non-sheath covered, surface of thedrug inserts 322, 324. In some examples, by controlling geometry of theexposed surface, a predetermined drug or agent release rate can beachieved. For instance, the exposed surface can be constructed with aspecific geometry or other technique appropriate to control the releaserate of the drug or other therapeutic agent onto an eye 100, such as onan acute basis or on a chronic basis, between outpatient doctor visits.Further description regarding effective release rates of one or moredrugs or other therapeutic agents from a drug insert 322, 324 can befound in commonly-owned DeJuan et al., U.S. patent application Ser. No.11/695,545, filed on Apr. 2, 2007 entitled “NASOLACRIMAL DRAINAGE SYSTEMIMPLANTS FOR DRUG THERAPY,” issued as U.S. Pat. No. 7,998,497 on Aug.16, 2011, and which is herein incorporated by reference in its entirety,including its description of obtaining particular release rates.

In some examples, such as is shown in FIG. 3B, the exposed surface ofthe drug insert 322, 324 can be flush or slightly below the proximal end308 of the first portion 304 or the distal end 310 of the second portion306, respectively, such that the drug insert does not protrude outsideof the implant body 302. In some examples, such as is shown in FIG. 4,the exposed surface of the first drug insert 322, for instance, can bepositioned above the proximal end 308 such that the first drug insert322 at least partially protrudes outside of the implant body 302.

The implant body 302 can include a graspable or other projection 332,such as one or more projections extending laterally at least partiallyfrom or around a proximal end 308 of the first implant body portion 304.In some examples, the graspable or other projection 332 can include aset of wings for use in inserting the lacrimal implant 300 into, orremoving the lacrimal implant 300 from, an implanted position. The setof wings or other projection 332 can be configured without migration inmind, as the non-linear configuration of the implant body 302 canprevent implant 300 migration by assuming a size or shape of thecanaliculus curvature 250 and optionally, the lacrimal canaliculusampulla 252 (FIG. 2). In some examples, the graspable or otherprojection 332 can be configured to seat against or near the punctalopening 212, 214, such as for inhibiting or preventing the lacrimalimplant 300 from passing completely within the lacrimal canaliculus 208,210, or for providing tactile or visual feedback information to animplanting user, e.g., as to whether the implant is fully implanted.

As shown in FIGS. 34A-34B, and discuss below, the graspable or otherprojection 332 can extend laterally in a direction parallel to or awayfrom an eye 100 when implanted. This may reduce irritation to the eye100 as compared to a case in which a portion of the projection extendstoward the eye 100. In addition, a lateral extension direction of theprojection 332 from the proximal end 308 can be substantially the sameas a lateral extension direction of the second implant body portion 306relative to the distal end 326 of the first implant body portion 304, asshown in FIGS. 3A-3B, for example. This can also avoid extension towardthe eye. The first drug insert 322 can partially extend though theregion of the projection 332, such as to provide sustained release of afirst drug or other therapeutic agent onto an eye.

In various examples, the implant body 302 can be molded using an elasticmaterial, such as silicone, polyurethane or other urethane-based polymeror copolymer, NuSil (e.g., NuSil 4840 with 2% 6-4800) or an acrylic of anon-biodegradable, partially biodegradable or biodegradable nature(i.e., erodeable within the body) allowing an implant body 302configured such that, when implanted in a lacrimal canaliculus 208, 210,an angled intersection 316 exists between a proximal 312 and distal 314axis to be formed. In some examples, the biodegradable elastic materialscan include cross-linked polymers, such as poly (vinyl alcohol). In someexamples, the implant body 302 can comprise a silicone/polyurethaneco-polymer. Other co-polymers that can be used to form the implant body302 include, but are not limited to, silicone/urethane, silicone/poly(ethylene glycol) (PEG), and silicone/2hydroxyethyl methacrylate (HEMA).As discussed in commonly-owned Utkhede et al., U.S. patent applicationSer. No. 12/23,986, filed on Sep. 5, 2008, entitled “DRUG CORES FORSUSTAINED RELEASE OF THERAPEUTIC AGENTS,” published as U.S. PatentApplication Publication No. 2009/0104243 on Apr. 23, 2009, and which isherein incorporated by reference in its entirety, urethane-based polymerand copolymer materials allow for a variety of processing methods andbond well to one another.

FIG. 3B illustrates an example of a cross-sectional view of the lacrimalimplant 300 taken along a line parallel to a longitudinal axis of theimplant, such as along line 3B-3B of FIG. 3A. As shown in FIG. 3B, thelacrimal implant 300 can include an implant body 302 including first 304and second 306 portions, and can extend from a proximal end 308 of thefirst portion 304 to a distal end 310 of the second portion 306. Invarious examples, the proximal end 308 can define a longitudinalproximal axis 312 and the distal end 310 can define a longitudinaldistal axis 314. The implant body 300 can be configured such that, whenimplanted, an at least 45 degree angled intersection 316 exists betweenthe proximal axis 312 and the distal axis 314 for biasing at least aportion of the implant body 302 against at least a portion of a lacrimalcanaliculus 208, 210 (FIG. 2) located at or more distal to a canaliculuscurvature 250 (FIG. 2). In this example, the implant body 300 isconfigured such that the angled intersection 316 is approximately about90 degrees.

In various examples, a distal end 326 of the first portion 304 can beintegral with the second portion 306 at or near a proximal end 328 ofthe second portion 306. In some examples, the second portion 306 caninclude a length having a magnitude less than four times a length of thefirst portion 304. In one example, the second portion 306 can include alength of less than about 10 millimeters and have a configured similarto that shown in FIG. 3B. In another example, the second portion 306 caninclude a length less than about 2 millimeters and have a configurationsimilar to that shown in FIG. 24.

In various examples, the second portion 306 can comprise an integraldilator 350 to dilate anatomical tissue 352, such as one or both of alacrimal punctum 212, 214 (FIG. 2) or associated canaliculus 208, 210,to a sufficient diameter as the lacrimal implant 300 is being implanted.In this way, the lacrimal implant 300 can be implanted in various sizeocular anatomies without the need for pre-dilation via a separateenlarging tool. The dilator 350 can be formed so as to not be traumaticto an inner lining of the punctum 212, 214 and the canaliculus 208, 210.In some examples, a lubricious coating disposed on, or impregnated in,an outer surface of the implant body 302 can be used to further aidinsertion of the lacrimal implant 300 into the anatomical tissue 352. Inone example, the lubricious coating can include a silicone lubricant.

As shown, the dilator 350 can generally narrow from a location near theproximal end 328 of the second portion 306 to the distal end 310 of thesecond portion 306, such as from a diameter of about 0.6 millimeters toa diameter of about 0.2 millimeters. In some examples, an outer surfaceslope of the dilator 350, as measured from the location near theproximal end 328 of the second portion 306 to the distal end 310 of thesecond portion 306, can be between about 1 degree and about 10 degrees(e.g., 2 degrees, 3 degrees, 4 degrees, or 5 degrees) with respect tothe longitudinal distal axis 314. In some examples, the slope of thedilator 350 can be less than 45 degrees with respect to the longitudinaldistal axis 314. Among other factors, a determination of a desirabledilator 350 slope for a given implant situation can be made by balancingan implant body 302 strength desirable for implantation with a desire tohave a soft, flexible and conforming implant body (e.g., to conform to alacrimal canaliculus anatomy) upon implantation. In some examples, adiameter of a dilator tip 354 can be between about 0.2 millimeters andabout 0.5 millimeters.

In certain examples, the proximal end 328 of the second implant bodyportion 306 can include a retention element 356 configured to biasagainst at least a portion of a lacrimal canaliculus ampulla 252 (FIG.2) when implanted. In this example, the retention element 356 projectsproximally from the intersection between the first 304 and second 306implant body portions, such as in an opposite direction as the extensionof the dilator 350. When present and implanted in the ampulla 252, theretention element 356 can help secure a seated position of the graspableor other projection 332 against the punctal opening 212, 214.

In certain examples, the implant body 302 includes a first cavity 318disposed near the proximal end 308. In this example, the first cavity318 extends inward about 2 millimeters or less from the proximal end308, and houses a first drug-releasing or other agent-releasing druginsert 322 to provide a sustained drug or other agent release to an eye.In some examples, the drug insert 322 can include a plurality oftherapeutic agent inclusions 360, which can be distributed in a matrix362. In some examples, the inclusions 360 can comprise a concentrated(e.g., crystalline) form of the therapeutic agent. In some examples, thematrix 362 can comprise a silicone matrix or the like, and thedistribution of inclusions 360 within the matrix can be substantiallyhomogenous or non-homogeneous. In some examples, the agent inclusions360 can include droplets of oil, such as Latanoprost oil. In still otherexamples, the agent inclusions 360 can comprise solid particles, such asBimatoprost particles in crystalline form. In some examples, the druginsert 322 comprises a urethane-based (e.g., polyurethane) polymer orcopolymer comprising therapeutic agent inclusions deliverable into theeye or surrounding tissues. The inclusions can be of many sizes andshapes. For instance, the inclusions can include microparticles havingdimensions on the order of about 1 micrometer to about 100 micrometers.Further discussion of drug-releasing or other agent-releasing druginserts can be found in commonly-owned Utkhede et al., U.S. patentapplication Ser. No. 12/23,986, filed on Sep. 5, 2008, entitled “DRUGCORES FOR SUSTAINED RELEASE OF THERAPEUTIC AGENTS,” published as U.S.Patent Application Publication No. 2009/0104243 on Apr. 23, 2009, andwhich is herein incorporated by reference in its entirety.

In various examples, the drug insert 322 can include a sheath body 366disposed over at least a portion of the insert to define at least oneinsert exposed surface 368. The exposed surface 368 can be located at ornear the proximal end 308 of the implant body 302, for example, therebyallowing direct contact with a tear or a tear film fluid and release ofa drug or other therapeutic agent from the drug insert 322 over asustained time period when the lacrimal implant 300 is inserted throughthe lacrimal punctum 212, 214 and into the associated canaliculus 208,210.

FIG. 4 illustrates an example of a side view of another integral dilator450 of an implant body 402 second portion 406 of a lacrimal implant 400.In this example, the dilator 450 narrows abruptly near a distal end 410of the second portion 406. As shown, an implant body first portion 404can include a first cavity 418 disposed near the proximal end 408. Inthis example, the first cavity 418 extends inward from the proximal end408, and houses a first drug-releasing or other agent-releasing druginsert 422 to provide a sustained drug or other therapeutic agentrelease to an eye, for instance. In some examples, the drug or othertherapeutic agent can released to an eye via an exposed, non-sheathcovered surface 468 of the drug insert 422. In this example, the exposedsurface 468 of the drug insert 422 is positioned above the proximal end408 such that the drug insert 422 at least partially protrudes outsideof the implant body 402.

In various examples, the outer surface 482 of the implant body 402 canbe formed, or surface treated to be, generally smooth to inhibitbacteria from attaching to the lacrimal implant 400 and incubating. Thegenerally smooth outer surface 482 can also prevent damage to the innerlining of the receiving anatomical tissue, such as a lacrimal punctum212, 214 (FIG. 2) or associated canaliculus 208, 210 (FIG. 2), duringimplantation. As further discussed in commonly-owned Rapacki et al.,U.S. patent application Ser. No. 12/283,002, filed Sep. 5, 2008,entitled “SURFACE TREATMENT OF IMPLANTS AND RELATED METHODS,” issued asU.S. Pat. No. 8,210,902 on Jul. 3, 2012, and which is hereinincorporated by reference in its entirety, the outer surface 482 of theimplant body 402 can be surface treated to be generally smooth via apolishing process. The polishing process can include causing a moldedimplant body 402 to be impacted with polishing media during an ongoingperiod of time in which the body 402 is in an enlarged, swelled state.This can smooth one or more surfaces or edges of the implant body 402.In various examples, the polishing media can include at least somegranules that are greater than about 3 millimeters in diameter.

In various examples, an antimicrobial coating 484 can be disposed on orimpregnated in at least a portion of the outer surface 482 to furtherprevent bacteria growth on the implant body 402. In some examples, theantimicrobial coating 484 can include an agent selected from the groupconsisting of 2-bromo-2-nitropropane-1,3-diol,5-bromo-5-nitro-1,3-dioxane, 7-ethyl bicyclooxazolidine, benzalkoniumchloride, benzethonium chloride, benzoic acid, benzyl alcohol, boricacid, bronopol, cetylpyridinium chloride, chlorhexidine digluconate,chloroacetamide, chlorobutanol, chloromethyl isothiazolinone and methylisothiazoline, dimethoxane, dimethyl oxazolidine, dimethyl hydroxymethylpyrazole, chloroxylenol, dehydroacetic acid, diazolidinyl urea,dichlorobenzyl alcohol, DMDM hydantoin, ethyl alcohol, formaldehyde,glutaraldehyde, hexachlorophene, hexetidine, hexamethylenetramine,imidazolidinyl urea, iodopropynyl butylcarbamate, isothiazolinones,methenammonium chloride, methyldibromo glutaronitrile, MDM hydantoin,minocycline, ortho phenylphenol, p-chloro-m-cresol, parabens(butylparaben, ethylparaben, methylparaben), phenethyl alcohol,phenoxyethanol, piroctane olamine, polyaminopropyl biguanide,polymethoxy bicyclic oxazolidine, polyoxymethylene, polyquaternium-42,potassium benzoate, potassium sorbate, propionic acid, quatemium-15,rifampin, salicylic acid, selenium disulfide, sodium borate, sodiumiodate, sodium hydroxymethylglycinate, sodium propionate, sodiumpyrithione, sorbic acid, thimerosal, triclosan, triclocarban,undecylenic acid, zinc phenosulfonate, and zinc pyrithione. In someexamples, the antimicrobial coating 484 can include a material selectedfrom the group consisting of silver lactate, silver phosphate, silvercitrate, silver acetate, silver benzoate, silver chloride, silveriodide, silver Iodate, silver nitrate, silver sulfadiazine, silverpalmitate, or one or more mixtures thereof. In some examples, theantimicrobial coating 484 can include at least one of an antibiotic oran antiseptic. For instance, the antimicrobial coating 484 can include atemporary anesthetic lasting, on average, between a few hours and a day.In still other examples, the antimicrobial coating 484 can include adrug or other therapeutic agent used to treat an underlying disease,such as a bolus, for immediate effect.

FIG. 5 illustrates an example of a schematic view of a lacrimal implant,such as the lacrimal implant 300 shown in FIG. 3, implanted in a lowerlacrimal punctum 214 and associated canaliculus 210. In some examples, alacrimal implant 300 can be implanted in an upper lacrimal punctum 212and canaliculus 208. As discussed above, the lacrimal implant 300 cancomprise an implant body 302 including first 304 and second 306portions. In various examples, the implant body 302 can be configuredsuch that, when implanted, at least a portion of the implant body 302 isbiased against at least a portion of the lacrimal canaliculus 210located at or more distal to a canaliculus curvature 250 to securelyretain an implanted position of the implant 300. As shown, the firstportion 304 can be configured to be inserted through the lacrimalpunctum 214 and into the associated canaliculus 210 and rest between thepunctal opening and a lacrimal canaliculus ampulla 252, while the secondportion 306 can be configured to insert through the lacrimal punctum 214and into the canaliculus 210 and rest between the ampulla 252 and thelacrimal sac 204. In certain examples, a retention element 356projecting from a proximal end of the second portion 306 can beconfigured to bias into and against at least a portion of the ampulla252 when implanted. In various examples, the first 304 and second 306portions can be configured to bend, stretch or collapse, as desired, tomaintain an adequate anatomical implanted fit without unduly stretchingocular anatomy.

In certain examples, to further secure an implant 300 within thelacrimal punctum 214 and canaliculus 210 or to make the implant body 302adjustable in size, a hydrogel or other fluid swellable material can bedisposed (e.g., coated) on an outer surface portion of the implant body302. The fluid swellable material can effectively expand an outersurface diameter portion of the implant body 302 when implanted. Incertain examples, the outer surface of the implant body 302 can includelongitudinal channels or grooves or coatings of a wicking material so asto allow fluid flow around the implant body 302. Using one or acombination of these techniques, a lacrimal implant 300 can beconfigured to completely occlude or only partially occlude the lacrimalcanaliculus 208, 210 when implanted therein. For instance, using thelongitudinal channels or grooves in one or both of the first 304 orsecond 306 portions of the implant body 302 can allow diminished volumesor tear drainage can occur, potentially facilitating the release of adrug or other therapeutic agent from a drug insert.

Forceps or another insertion tool can be used to implant the lacrimalimplant 300 through the lacrimal punctum 212, 214 and into theassociated canaliculus 208, 210. In some examples, an insertion tool asdiscussed in commonly-owned De Juan, et al., U.S. patent applicationSer. No. 12/231,984, filed on Sep. 5, 2008, entitled “INSERTION ANDEXTRACTION TOOLS FOR LACRIMAL IMPLANTS,” published as U.S. PatentApplication Publication No. 2009/0105749 on Apr. 23, 2009, and which isherein incorporated by reference in its entirety, can be used to implantthe lacrimal implant 300. In various examples, the second portion 306 ofthe implant body 302 can be advanced into the depth of the lacrimalcanaliculus 208, 210 by manipulation of the inserter tool until agraspable or other projection 332, if present, can be seated against thepunctal opening 212, 214. When it is desired to remove the lacrimalimplant 300, the projection 332 can be grasped with the forceps, forexample, and withdrawn from the punctal opening 212, 214.

In certain examples, the implant body 302 can include one or both of afirst cavity 318 disposed near the proximal end 308 or a second cavity320 disposed near the distal end 310. In this example, the first cavity318 extends inward from the proximal end 308 of the first portion 304,and the second cavity 320 extends inward from the distal end 310 of thesecond portion 306. A first drug-releasing or other agent-releasing druginsert 322 can be disposed in the first cavity 318 to provide asustained drug or other therapeutic agent release to the eye (e.g., totreat an infection, inflammation, glaucoma or other ocular disease ordisorder), while a second drug-releasing or other agent-releasing druginsert 324 can be disposed in the second cavity 320 to provide asustained drug or other therapeutic agent release to the nasal passage(e.g., to treat a sinus or allergy disorder) or inner ear system (e.g.,to treat dizziness or a migraine), for example.

FIGS. 6A-6B illustrate an example of another lacrimal implant 600 thatis insertable through a lacrimal punctum 212, 214 and into theassociated canaliculus 208, 210 (FIG. 2). In this example, the lacrimalimplant 600 can comprises an implant body 602 including first 604 andsecond 606 portions, and can extend from a proximal end 608 of the firstportion 604 to a distal end 610 of the second portion 606. The proximalend 608 can define a longitudinal proximal axis 612 and the distal end610 can define a longitudinal distal axis 614. The implant body 600 canbe configured such that, when implanted, an angled intersection ofapproximately 90 degrees exists between the proximal axis 612 and thedistal axis 614 for biasing at least a portion of the implant bodyagainst at least a portion of the lacrimal canaliculus 208, 210 (FIG. 2)located at or more distal to a canaliculus curvature 250 (FIG. 2).

In this example, a proximal end 628 of the second implant body portion606 can include a retention element 656 configured to bias against atleast a portion of a lacrimal canaliculus ampulla 252 (FIG. 2) whenimplanted. In this example, the implant body 602 includes a first cavity618, configured to receive a first drug-releasing or otheragent-releasing drug insert, disposed near the proximal end 608 of thefirst implant body portion 604. Also in this example, the implant body602 can include a graspable or other projection 632, such as a set ofwings having a combined length of about 1 millimeter, for example, andextending laterally from the proximal end 308.

FIG. 6B illustrates an example of a cross-sectional view of the lacrimalimplant 600 taken along a line parallel to a longitudinal axis of theimplant, such as along line 6B-6B of FIG. 6A. As shown in FIG. 6B, adistal end 626 of the first portion 604 can be integral with the secondportion 606 at or near a proximal end 628 of the second portion 606. Invarious examples, the second portion 606 can include a longitudinallength, as measured from the proximal axis 612 to the distal end 610,having a magnitude less than four times a longitudinal length of thefirst portion 604, as measured from the proximal end 608 to the distalaxis 614. In some examples, the first portion can include a longitudinallength of about 1.54 millimeters and the second portion can include alongitudinal length of between about 4.5 millimeters to about 5.42millimeters.

In various examples, the second portion 606 can comprise an integraldilator 650 to dilate anatomical tissue, such as one or both of thelacrimal punctum 212, 214 (FIG. 2) or associated canaliculus 208, 210,to a sufficient diameter as the lacrimal implant 600 is being implanted.In some examples, the second portion 606 tapers from a diameter of theproximal end of between about 0.50 millimeters to about 0.75 millimetersto a dilator tip 654 diameter of about 0.36 millimeters.

FIGS. 7A-7B illustrate an example of another lacrimal implant 700 thatis insertable through a lacrimal punctum 212, 214 and into theassociated canaliculus 208, 210 (FIG. 2). In this example, the lacrimalimplant 700 can comprises an implant body 702 including first 704 andsecond 706 portions, and can extend from a proximal end 708 of the firstportion 704 to a distal end 710 of the second portion 706. The proximalend 708 can define a longitudinal proximal axis 712 and the distal end710 can define a longitudinal distal axis 714. The implant body 700 canbe configured such that, when implanted, an angled intersection ofapproximately 90 degrees exists between the proximal axis 712 and thedistal axis 714 for biasing at least a portion of the implant bodyagainst at least a portion of the lacrimal canaliculus 208, 210 (FIG. 2)located at or more distal to a canaliculus curvature 250 (FIG. 2). Asshown in the example of FIG. 7A, a smooth transition can exist betweenthe first 704 and second 706 portions.

In this example, the implant body 702 includes a first cavity 718configured to receive a first drug-releasing or other agent-releasingdrug insert, disposed near the proximal end 708 of the first implantbody portion 704. Also in this example, the implant body 702 can includea graspable or other projection 732, such as an annular projectionextending laterally from, and completely around, the proximal end 708.In some examples, the graspable or other projection 732 includes apartially trimmed projection having a trimmed width of about 0.75millimeters and extending varying amounts around the proximal end 708.

FIG. 7B illustrates an example of a cross-sectional view of the lacrimalimplant 700 taken along a line parallel to a longitudinal axis of theimplant, such as along line 7B-7B of FIG. 7A. As shown in FIG. 7B, adistal end 726 of the first portion 704 can be integral with the secondportion 706 at or near a proximal end 728 of the second portion 706. Invarious examples, the second portion 706 can include a longitudinallength, as measured from the proximal axis 712 to the distal end 710,having a magnitude less than four times a longitudinal length of thefirst portion 704, as measured from the proximal end 708 to the distalaxis 714. In some examples, the first portion can include a longitudinallength of about 1.5 millimeters and the second portion can include alongitudinal length of about 5 millimeters.

In various examples, the second portion 706 can comprise an integraldilator 750 to dilate anatomical tissue, such as one or both of thelacrimal punctum 212, 214 (FIG. 2) or associated canaliculus 208, 210,to a sufficient diameter as the lacrimal implant 700 is being implanted.In some examples, the second portion 706 tapers from a diameter of theproximal end of about 0.46 millimeters to a dilator tip 754 diameter ofabout 0.36 millimeters.

FIGS. 8A-8B illustrate an example of another lacrimal implant 800 thatis insertable through a lacrimal punctum 212, 214 and into theassociated canaliculus 208, 210 (FIG. 2). In this example, the lacrimalimplant 800 can comprises an implant body 802 including first 804 andsecond 806 portions, and can extend from a proximal end 808 of the firstportion 804 to a distal end 810 of the second portion 806. The proximalend 808 can define a longitudinal proximal axis 812 and the distal end810 can define a longitudinal distal axis 814. The implant body 800 canbe configured such that, when implanted, an angled intersection ofapproximately 90 degrees exists between the proximal axis 812 and thedistal axis 814 for biasing at least a portion of the implant bodyagainst at least a portion of the lacrimal canaliculus 208, 210 (FIG. 2)located at or more distal to a canaliculus curvature 250 (FIG. 2).

In this example, a proximal end 828 of the second implant body portion806 can include a retention element 856 configured to bias against atleast a portion of a lacrimal canaliculus ampulla 252 (FIG. 2) whenimplanted. The retention element 856 can include aninsertion-facilitating depression 875 or other gripping means to aid inone or both of implant insertion or removal. In this example, theimplant body 802 includes a first cavity 818 configured to receive afirst drug-releasing or other agent-releasing drug insert, disposed nearthe proximal end 808 of the first implant body portion 804. Also in thisexample, the implant body 802 can include a graspable or otherprojection 832, such as an annular projection extending laterally from,and completely around, the proximal end 808. In some examples, thegraspable or other projection 832 includes a partially trimmedprojection extending varying amounts around the proximal end 808.

FIG. 8B illustrates an example of a cross-sectional view of the lacrimalimplant 800 taken along a line parallel to a longitudinal axis of theimplant, such as along line 8B-8B of FIG. 8A. As shown in FIG. 8B, adistal end 826 of the first portion 804 can be integral with the secondportion 806 at or near the proximal end 828 of the second portion 806.In various examples, the second portion 806 can include a longitudinallength, as measured from the proximal axis 812 to the distal end 810,having a magnitude less than four times a longitudinal length of thefirst portion 804, as measured from the proximal end 808 to the distalaxis 814. In some examples, the first portion can include a longitudinallength of between about 1.725 millimeters to about 1.77 millimeters andthe second portion can include a longitudinal length of between about4.77 millimeters to about 5 millimeters.

In various examples, the second portion 806 can comprise an integraldilator 850 to dilate anatomical tissue, such as one or both of thelacrimal punctum 212, 214 (FIG. 2) or associated canaliculus 208, 210,to a sufficient diameter as the lacrimal implant 800 is being implanted.In some examples, the second portion 806 tapers from a diameter of theproximal end 828 of about 0.46 millimeters to a dilator tip 854 diameterof about 0.36 millimeters.

FIG. 9 illustrates an example of another lacrimal implant 900 that isinsertable through a lacrimal punctum 212, 214 and into the associatedcanaliculus 208, 210 (FIG. 2). In this example, the lacrimal implant 900can comprises an implant body 902 including first 904 and second 906portions, and can extend from a proximal end 908 of the first portion904 to a distal end 910 of the second portion 906. The proximal end 908can define a longitudinal proximal axis 912 and the distal end 910 candefine a longitudinal distal axis 914. The implant body 900 can beconfigured such that, when implanted, an angled intersection ofapproximately 90 degrees exists between the proximal axis 912 and thedistal axis 914 for biasing at least a portion of the implant bodyagainst at least a portion of the lacrimal canaliculus 208, 210 (FIG. 2)located at or more distal to a canaliculus curvature 250 (FIG. 2).

As shown, a smooth transition can exist between the first 904 and second906 portions. In this example, the smooth transition can include aninsertion-facilitating depression 975 or other gripping means to aid inone or both of implant insertion or removal. Also in this example, theimplant body 902 can include a graspable or other projection 932, suchas an annular projection extending laterally from, and completelyaround, the proximal end 908. In some examples, the graspable or otherprojection 932 includes a partially trimmed projection extending varyingamounts around the proximal end 908.

FIGS. 10A-10B illustrate an example of another lacrimal implant 1000that is insertable through a lacrimal punctum 212, 214 and into theassociated canaliculus 208, 210 (FIG. 2). In this example, the lacrimalimplant 1000 can comprises an implant body 1002 including first 1004 andsecond 1006 portions, and can extend from a proximal end 1008 of thefirst portion 1004 to a distal end 1010 of the second portion 1006. Theproximal end 1008 can define a longitudinal proximal axis 1012 and thedistal end 1010 can define a longitudinal distal axis 1014. The implantbody 1000 can be configured such that, when implanted, an angledintersection of approximately 90 degrees exists between the proximalaxis 1012 and the distal axis 1014 for biasing at least a portion of theimplant body against at least a portion of the lacrimal canaliculus 208,210 (FIG. 2) located at or more distal to a canaliculus curvature 250(FIG. 2).

In this example, a proximal end 1028 of the second implant body portion1006 can include a retention element 1056 configured to bias against atleast a portion of a lacrimal canaliculus ampulla 252 (FIG. 2) whenimplanted. The retention element 1056 can include aninsertion-facilitating depression 1075 or other gripping means to aid inone or both of implant insertion or removal. In this example, theimplant body 1002 includes a first cavity 1018 configured to receive afirst drug-releasing or other agent-releasing drug insert, disposed nearthe proximal end 1008 of the first implant body portion 1004. Also inthis example, the implant body 1002 can include a graspable or otherprojection 1032, such as an annular projection having a diameter ofabout 1.3 millimeters extending laterally from, and completely around,the proximal end 1008. In some examples, the graspable or otherprojection 1032 includes a partially trimmed projection extendingvarying amounts around the proximal end 1008.

FIG. 10B illustrates an example of a cross-sectional view of thelacrimal implant 1000 taken along a line parallel to a longitudinal axisof the implant, such as along line 10B-10B of FIG. 10A. As shown in FIG.10B, a distal end 1026 of the first portion 1004 can be integral withthe second portion 1006 at or near a proximal end 1028 of the secondportion 1006. In various examples, the second portion 1006 can include alongitudinal length, as measured from the proximal axis 1012 to thedistal end 1010, having a magnitude less than four times a longitudinallength of the first portion 1004, as measured from the proximal end 1008to the distal axis 1014. In some examples, the first portion can includea longitudinal length of about 1.5 millimeters and the second portioncan include a longitudinal length of about 5 millimeters.

In various examples, the second portion 1006 can comprise an integraldilator 1050 to dilate anatomical tissue, such as one or both of thelacrimal punctum 212, 214 (FIG. 2) or associated canaliculus 208, 210,to a sufficient diameter as the lacrimal implant 1000 is beingimplanted. In some examples, the second portion 1006 tapers from aproximal end 1028 diameter of about 0.46 millimeters to a dilator tip1054 diameter of about 0.36 millimeters.

FIGS. 11-17 illustrate examples of other lacrimal implants 1100, 1200,1300, 1400, 1500, 1600, 1700 that are insertable through a lacrimalpunctum 212, 214 and into the associated canaliculus 208, 210 (FIG. 2).In these examples, each lacrimal implant 1100, 1200, 1300, 1400, 1500,1600, 1700 can comprises an implant body 1102, 1202, 1302, 1402, 1502,1602, 1702 including first 1104, 1204, 1304, 1404, 1504, 1604, 1704 andsecond 1106, 1206, 1306, 1406, 1506, 1606, 1706 portions, and can extendfrom a proximal end 1108, 1208, 1308, 1408, 1508, 1608, 1708 of thefirst portion 1104, 1204, 1304, 1404, 1504, 1604, 1704 to a distal end1110, 1210, 1310, 1410, 1510, 1610, 1710 of the second portion 1106,1206, 1306, 1406, 1506, 1606, 1706. Each implant body 1102, 1202, 1302,1402, 1502, 1602, 1702 can include at least one intermediately-disposedretainment projection 1192, 1292, 1392, 1492, 1592, 1692, 1792 topotentially further secure an implanted position of the lacrimalimplants. The intermediately-disposed retainment projections 1192, 1292,1392, 1492, 1592, 1692, 1792 can be positioned on one or both of thefirst 1104, 1204, 1304, 1404, 1504, 1604, 1704 or second 1106, 1206,1306, 1406, 1506, 1606, 1706 implant body portions, and can take theform of annular, semi-annular, column-like or barrel-like projection.The intermediately-disposed retainment projections 1192, 1292, 1392,1492, 1592, 1692, 1792 can include a cross-sectional size greater thanan adjacent implant body portion and can slightly deform a portion of acanalicular wall to provide the added securement.

It is believed that the occlusion of the lower lacrimal canaliculus 210,for example, by a lacrimal implant may cause back pressure to build-upwithin the canaliculus 210, thereby urging the implant from an implantedposition. It is thought that this back pressure could, for example,occur during a blink (where tears are being pumped from an anteriorsurface of the eye down a drainage system) or a sneeze (where pressureis emanating up from the pulmonary system). Accordingly, one of more ofthe additional retention features now shown in the form of at least oneintermediately-disposed retainment projection 1192, 1292, 1392, 1492,1592, 1692, 1792 may be used to prevent implant migration and furthersecure an implanted lacrimal implant position. These additionalretention features can be designed to prevent migration in the proximaldirection while not increasing implant implantation difficultly.

FIGS. 18-19 illustrate examples of other lacrimal implants 1800, 1900that are insertable through a lacrimal punctum 212, 214 and into theassociated canaliculus 208, 210 (FIG. 2). In these examples, eachlacrimal implant 1800, 1900 can comprise an implant body 1802, 1902including first 1804, 1904 and second 1806, 1906 portions, and canextend from a proximal end 1808, 1908 of the first portion 1804, 1904 toa distal end 1810, 1910 of the second portion 1806, 1906. As shown, anintermediate portion 1896, 1996 of each implant body 1802, 1902 can beangled relative to one or both of the first 1804, 1904 or second 1806,1906 implant body portions to potentially further secure an implantedposition of the lacrimal implants.

It is believed that the angling of the intermediate portion 1896, 1996may help capture the anatomy of the lacrimal punctum 212, 214 andcanaliculus 208, 210 to keep the lacrimal implants 1800, 1900 in animplanted position, such as via a directional force applied by theangling against the lacrimal canaliculus. This directional force can bedesigned to continuously urge a feedback or other projection 1832, 1932flush with the punctum 212, 214.

FIG. 20 illustrates an example of another lacrimal implant 2000 that isinsertable through a lacrimal punctum 212, 214 and into the associatedcanaliculus 208, 210 (FIG. 2). In this example, the lacrimal implant2000 can comprises an implant body 2002 including first 2004 and second2006 portions, and can extend from a proximal end 2008 of the firstportion 2004 to a distal end 2010 of the second portion 2006. Theproximal end 2008 can define a longitudinal proximal axis 2012 and thedistal end 2010 can define a longitudinal distal axis 2014. The implantbody 2000 can be configured such that, when implanted, an angledintersection of approximately 90 degrees exists between the proximalaxis 2012 and the distal axis 2014 for biasing at least a portion of theimplant body against at least a portion of a lacrimal canaliculus 208,210 (FIG. 2) located at or more distal to a canaliculus curvature 250(FIG. 2). In various examples, a distal end 2026 of the first portion2004 can be integral with the second portion 2006 at or near a proximalend 2028 of the second portion 2006.

In this example, one or more material cutouts 2080 are made in an outersurface of the implant body 2002. As a result, the angled intersectionbetween the proximal axis 2012 and the distal axis 2014 can become morelinearly aligned during implant, as shown in phantom, to facilitateinsertion through the lacrimal punctum 212, 214 and into the associatedcanaliculus 208, 210.

FIGS. 21A-21B and 22A-22B illustrate examples of a side view of otherlacrimal implants 2100, 2200 that are insertable through a lacrimalpunctum 212, 214 and into the associated canaliculus 208, 210 (FIG. 2).In these examples, each lacrimal implant 2100, 2200 can comprises animplant body 2102, 2202 including first 2104, 2204 and second 2106, 2206portions, and can extend from a proximal end 2108, 2208 of the firstportion 2104, 2204 to a distal end 2110, 2210 of the second portion2106, 2206. Each second portion 2106, 2206 can include one or more armmembers 2170, 2270 movable between a first configuration, in which theone or more arm members 2170, 2270 are adjacent the implant body, and asecond configuration, in which the one or more arm members 2170, 2270laterally extend from a side of the implant body. In the firstconfiguration, the one or more arm members 2170, 2270 facilitateinsertion of the lacrimal implant through the lacrimal punctum 212, 214and into the associated canaliculus 208, 210 by providing a narrowprofile. In the second configuration, the one or more arm members 2170,2270 laterally extend to fill at least one of a lacrimal canaliculusampulla 252 (FIG. 2) or the canaliculus 208, 210 when implanted.Optionally, the one or more arm members 2170, 2270 can include a fluidswellable material, such as hydrogel, to further secure an implantedlacrimal implant within the lacrimal ampulla 252 or canaliculus 208, 210when hydrated.

In some examples, the one or more arm members 2170, 2270 can beincorporated into a mold that is also used to form the implant body2102, 2202. The one or more arm members 2170, 2270 can alternatively beattached by molding or gluing onto an existing implant body 2102, 2202.Different thicknesses and shapes for the one or more arm members 2170,2270 can be employed for different stiffness and securing/removalcharacteristics. Beyond hydrogel, the one or more arm members 2170, 2270can be made of other materials, such as those used for the haptics onthe intraocular lenses or the like.

FIG. 23A-23B illustrate an example of a side view of another lacrimalimplant 2300 that is insertable through a lacrimal punctum 212, 214 andinto the associated canaliculus 208, 210 (FIG. 2). In this example, thelacrimal implant 2300 can comprises an implant body 2302 including first2304 and second 2306 portions, and can extend from a proximal end 2308of the first portion 2304 to a distal end 2310 of the second portion2306. The second portion 2306 can be surrounded, at least in part, by anexpandable retention element (e.g., an inflatable balloon) 2372, whichis configured to bias the second portion 2306 away from a lacrimalcanaliculus wall upon expansion.

In some examples, the expandable retention element 2372 contains or canbe inflated by an agent to be delivered to a tissue of the eye ornasolacrimal system. In some examples, the expandable retention element2372 can employ one or more balloons which are separate from any druginsert or other agent retaining structure. The one or more balloons mayoptionally be similar to those used on balloon catheters, with aninflation lumen or the like optionally being included in an implantinsertion tool so as to allow controlled inflation of the balloon. Insuch an example, the lacrimal implant 2300 may be inserted with theballoons deflated, as shown in FIG. 23A. Once the lacrimal implant 2300is in place, the balloons can then inflated to secure an implantedposition of the implant, as shown in FIG. 23B.

The balloons can also be deflatable to make removal of the lacrimalimplant 2300 easier. The balloons can optionally partially orsubstantially conform to variations in the size and shape of thecanaliculus 208, 210. Alternative examples of balloons may be inflatedby swelling of a material disposed within the balloon, such as swellingof a hydrogel by absorption of water through perforations or openings inthe balloon. The one or more balloons can be annular structures disposedaround the supporting implant body, or may be disposed eccentricallyabout an axis of the implant body. As illustrated in FIG. 23B, theballoons may be disposed sufficiently distal to reside within oradjacent a horizontal portion of the tear drainage duct, within oradjacent a lacrimal ampulla of the tear drainage system, or the like.Alternative examples can include one or more balloons which are moreproximal.

FIG. 24 illustrates an example of a schematic view of another lacrimalimplant 2400 implanted through a lower lacrimal punctum 214 and into theassociated canaliculus 210. The lacrimal implant 2400 can comprise animplant body 2402 including first 2404 and second 2406 portions. Invarious examples, the implant body 2402 can be configured such that,when implanted, at least a portion of the implant body 2402 is biasedagainst at least a portion of the lacrimal canaliculus 210 located at ormore distal to a canaliculus curvature 250 to securely retain animplanted position of the implant 2400. In this example, the secondportion 2406 includes a longitudinal length less than about 2millimeters, such as a size greater than a diameter of the first portion2404, but less than 2 millimeters. Also in this example, the implantbody 2402 can include a graspable or other projection 2432, such asextending laterally at least partially around a proximal end of thefirst implant body portion 2404.

FIGS. 25A-25B illustrate examples of another lacrimal implant 2500 thatis insertable through a lacrimal punctum 212, 214 and into theassociated canaliculus 208, 210 (FIG. 2). In these examples, thelacrimal implant 2500 can comprise an implant body 2502 including first2504 and second 2506 portions, and can extend from a proximal end 2508of the first portion 2504 to a distal end 2510 of the second portion2506. The implant body can include a general shape, which can generallymatch the anatomical features of a canaliculus 208, 210 to providepatient comfort and secure retainment, for example. The proximal end2508 can define a longitudinal proximal axis 2512 and the distal end2510 can define a longitudinal distal axis 2514. The implant body 2502can be configured such that, when implanted, an angled intersection ofbetween 45-90 degrees exists between the proximal axis 2512 and thedistal axis 2514 such as for biasing at least a portion of the implantbody 2502 against at least a portion of a lacrimal canaliculus 208, 210(FIG. 2) located at or more distal to a canaliculus curvature 250 (FIG.2).

In the examples of FIGS. 25A-25B, the implant body 2502 includes both ofa first cavity 2518 disposed near the proximal end 2508 and a secondcavity 2520 disposed near the distal end 2510. The first cavity 2518extends inward from the proximal end 2508 of the first portion 2504, andthe second cavity 2520 extends inward from the distal end 2510 of thesecond portion 2506. A first drug-releasing or other agent-releasingdrug insert can be disposed in the first cavity 2518 to provide asustained drug or other therapeutic agent release to an eye, while asecond drug-releasing or other agent-releasing drug insert can bedisposed in the second cavity 2520 to provide a sustained drug or othertherapeutic agent release to a nasal passage or inner ear system, forexample. In some examples, the first cavity 2518 can extend inward fromthe proximal end 2508 of the first portion 2504 to a position near thedistal end 2510 of the second portion 2506, such as is shown in FIG. 26,and is filled with a first drug-releasing or other agent-releasing druginsert. In some examples, the second cavity 2520 can extend inward fromthe distal end 2510 of the second portion 2506 to a position near theproximal end 2508 of the first portion 2504 and is filled with a seconddrug-releasing or other agent-releasing drug insert.

In certain examples, the second portion 2506 comprises an integraldilator 2550 to dilate anatomical tissue, such one or both of thelacrimal punctum 212, 214 or canaliculus 208, 210, to a sufficientdiameter as the lacrimal implant 2500 is being implanted. In this way,the lacrimal implant 2500 can be implanted in various size ocularanatomies without the need for pre-dilation via a separate enlargingtool. In these examples, the integral dilator 2550 includes a generallyconcave shape related to the first portion 2504. In some examples, theconcave shape includes a radius less than a radius of the canaliculuscurvature 250. In some examples, the concave shape includes a radiussubstantially the same as the radius of the canaliculus curvature 250.As shown in the example of FIG. 25B, a smooth transition can existbetween the first 2504 and second 2506 portions.

In certain examples, a proximal end 2528 of the second implant bodyportion 2506 can include a retention element 2556 configured to biasagainst at least a portion of a lacrimal canaliculus ampulla 252 (FIG.2) when implanted. In the example of FIG. 25A, the retention element2556 projects proximally from the intersection between the first 2504and second 2506 implant body portions.

FIG. 26 illustrates an example of another lacrimal implant 2600 that isinsertable through a lacrimal punctum 212, 214 and into the associatedcanaliculus 208, 210 (FIG. 2). In this example, the lacrimal implant2600 comprises an implant body 2602 including first 2604 and second 2606portions, and extends from a proximal end 2608 of the first portion 2604to a distal end 2610 of the second portion 2606. The proximal end 2608can define a longitudinal proximal axis 2612 and the distal end 2610 candefine a longitudinal distal axis 2614. The implant body 2600 can beconfigured such that, when implanted, an angled intersection of between90-135 degrees exists between the proximal axis 2612 and the distal axis2614 for biasing at least a portion of the implant body against at leasta portion of a lacrimal canaliculus 208, 210 located at or more distalto a canaliculus curvature 250 (FIG. 2).

In certain examples, the implant body 2602 can include a first cavity2618 disposed near the proximal end 2608. In this example, the firstcavity 2618 extends inward from the proximal end 2608 of the firstportion 2604 to a position near the distal end 2610 of the secondportion 2606. A first drug-releasing or other agent-releasing druginsert having a volume between about 0.2 cubic centimeters to about 0.25cubic centimeters, for example, can be disposed in the first cavity 2618to provide a extended sustained drug or other therapeutic agent releaseto an eye.

In certain examples, the second portion 2606 comprises an integraldilator 2650 to dilate anatomical tissue, such one or both of thelacrimal punctum 212, 214 or canaliculus 208, 210, to a sufficientdiameter as the lacrimal implant 2600 is being implanted. In this way,the lacrimal implant 2600 can be implanted in various size ocularanatomies without the need for pre-dilation via a separate enlargingtool. In this example, the dilator 2650 includes a generally convexshape relative to the first portion 2604. In some examples, the convexshape includes a radius less than a radius of the canaliculus curvature250. In some examples, the convex shape includes a radius substantiallythe same as the radius of the canaliculus curvature 250.

In certain examples, a proximal end 2628 of the second implant bodyportion 2606 can include a retention element 2656 configured to biasagainst at least a portion of a lacrimal canaliculus ampulla 252 (FIG.2) when implanted. In this example, the retention element 2656 projectsproximally from the intersection between the first 2604 and second 2606implant body portions. In some examples, such as is shown in FIGS.29-30, a proximal end 2628 of the second implant body portion 2606 caninclude a retention element 2656 comprising a hydrogel retentionelement, which is configured to expand into the ampulla 252 when theimplant body 2602 is implanted.

FIG. 27 illustrates an example of a side view of another lacrimalimplant 2700 that is insertable through a lacrimal punctum 212, 214 andinto the associated canaliculus 208, 210 (FIG. 2). In this example, thelacrimal implant 2700 comprises an implant body 2702 including first andsecond portions, which prior to implant, are linear relative to oneanother. The implant body 2702 extends from a proximal end 2708 of thefirst portion to a distal end 2710 of the second portion. The proximalend 2708 can define a longitudinal proximal axis 2712 and the distal end2710 can define a longitudinal distal axis 2714. The implant body 2702can be configured such that, when implanted, an angled intersection ofbetween 45-135 degrees exists between the proximal axis 2712 and thedistal axis 2714 such as for biasing at least a portion of the implantbody 2702 against at least a portion of a lacrimal canaliculus 208, 210(FIG. 2) located at or more distal to a canaliculus curvature 250 (FIG.2). In this example, the second portion of the implant body 2702includes at least one undulation 2790 to facilitate the biasing of theimplant body 2702 against the portion of the lacrimal canaliculus 208,210.

FIG. 28 illustrates an example of a side view of another lacrimalimplant 2800 that is insertable through a lacrimal punctum 212, 214 andinto the associated canaliculus 208, 210 (FIG. 2). In this example, thelacrimal implant 2800 comprises an implant body 2802 including first andsecond portions, which prior to implant, are linear relative to oneanother. The implant body 2802 extends from a proximal end 2808 of thefirst portion to a distal end 2810 of the second portion. The proximalend 2808 can define a longitudinal proximal axis 2812 and the distal end2810 can define a longitudinal distal axis 2814. The implant body 2802can be configured such that, when implanted, an angled intersection ofbetween 45-135 degrees exists between the proximal axis 2812 and thedistal axis 2814 for biasing at least a portion of the implant body 2802against at least a portion of a lacrimal canaliculus 208, 210 (FIG. 2)located at or more distal to a canaliculus curvature 250 (FIG. 2). Inthis example, the second portion of the implant body 2802 includes atleast one intermediately-disposed retainment projection 2892, such anannular rib-like projection. The retainment projection 2892 includes across-sectional size greater than an adjacent implant body portion andcan facilitate the securement of an implanted position of the implantbody 2802, while the adjacent narrower implant body portion canfacilitate the biasing of the implant body 2802 against the portion ofthe lacrimal canaliculus 208, 210.

FIGS. 29-32 illustrate examples of a side view of other lacrimalimplants 2900, 3000, 3100, 3200 that are insertable through a lacrimalpunctum 212, 214 and into the associated canaliculus 208, 210 (FIG. 2).In these examples, each lacrimal implant 2900, 3000, 3100, 3200 cancomprise an implant body 2902, 3002, 3102, 3202 including first 2904,3004, 3104, 3204 and second 2906, 3006, 3106, 3206 portions, and canextend from a proximal end 2908, 3008, 3108, 3208 of the first portion2904, 3004, 3104, 3204 to a distal end 2910, 3010, 3110, 3210 of thesecond portion 2906, 3006, 3106, 3206. The proximal end 2908, 3008,3108, 3208 can define a longitudinal proximal axis 2912, 3012, 3112,3212.

The second portion 2906, 3006, 3106, 3206 can include a fluid swellableretention element 2994, 3094, 3194, 3294 configured to expand laterally,relative to the proximal axis 2912, 3012, 3112, 3212, when the implantbody 2902, 3002, 3102, 3202 is implanted. In various examples, the fluidswellable retention element 2994, 3094, 3194, 3294 can be formed suchthat one or both of expansion direction or expansion amount can becontrolled. For instance, the fluid swellable retention element 2994,3094, 3194, 3294 can expand more in one plane than another to securelyanchor the lacrimal implants. In some examples, the fluid swellableretention element 2994, 3094, 3194, 3294 includes a portion configuredto expand laterally, relative to the proximal axis 2912, 3012, 3112,3212, in a direction away from a lacrimal canaliculus ampulla 252 (FIG.2) when the implant body is implanted. In some examples, as shown inFIGS. 29-30, the fluid swellable retention element 2994, 3094, 3194,3294 includes a portion configured to expand laterally, relative to theproximal axis 2912, 3012, 3112, 3212, in a direction toward the lacrimalcanaliculus ampulla 252 (FIG. 2) when the implant body is implanted.

In some examples, the fluid swellable retention element 2994, 3094,3194, 3294 can comprise hydrogel, which is insertable through thelacrimal punctum 212, 214 and into the associated canaliculus 208, 210in a narrow profile. After insertion, the hydrogel or other fluidswellable retention element can hydrate and expand to a wideconfiguration. Protrusions, such as at least one intermediately-disposedretainment projection 2992, 3092, 3192, 3292, can be used to retain toan implanted position of the lacrimal implants while the hydrogel orother swellable element expands.

FIG. 33 illustrates an example of a side view of another lacrimalimplant 3300 that is insertable through a lacrimal punctum 212, 214 andinto the associated canaliculus 208, 210 (FIG. 2). In this example, thelacrimal implant 3300 can comprise an implant body 3302 including first3304 and second 3306 portions, and can extend from a proximal end 3308of the first portion 3304 to a distal end 3310 of the second portion3306. As shown, the second portion 3306 can include an expandableretention element 3393 comprising at least one of a coil, a braid, astent, a mesh tube, a suture, a thermoset polymer, a thermoplastic, aheat activatable material, or a shape memory material. The expandableretention element 3393 can be configured to expand laterally, relativeto a proximal axis 3312 defined by the first portion 3304, when theimplant body is implanted. Protrusions, such as at least oneintermediately-disposed retainment projection 3392, can be used topotentially further secure an implanted position of the lacrimalimplant.

FIGS. 34A-34B illustrate examples of a schematic view of anotherlacrimal implant 3400 and an implant environment. In various examples,the implant body 3402 can include a graspable or other projection 3432,such as one or more projections extending laterally at least partiallyfrom or around a proximal end 3408 of a first implant body portion. Insome examples, such as is shown in FIG. 34B, the projections 3432 caninclude a set of wings for use in inserting the lacrimal implant 3400into, or removing the implant from, an implanted position. The set ofwings can be configured without migration in mind, as the implanted,non-linear configuration of the implant body 3402 can prevent migrationby assuming a size or shape of a canaliculus curvature 250 andoptionally, a lacrimal canaliculus ampulla 252.

In the examples of FIGS. 34A-34B, the one or more projections 3432extend laterally in a direction parallel to or away from an eye 100 whenimplanted. In this way, the projections 3432 can still act as agraspable or feedback feature, but can limit patient discomfort when thelacrimal implant 3400 is implanted. In addition, the projections 3432,by extending away from the eye 100, may not be buried in tissue and maybe easily recognized by the patient or physician. This can allow for aquick determination if the lacrimal implant 3400 is being retained inits proper place without having to dig and search in the soft tissuesurrounding the eye 100. In some instances, a simple pull on the lowereyelid can expose the projection 3432 pointed in a direction away fromthe eye 100. In the example of FIG. 34B, a lateral extension of at leastone projection 3432 from the proximal end 3408 is substantially the sameas a lateral extension direction of a second implant body portionrelative to a distal end of the first implant body portion.

FIGS. 35-38 illustrate examples of an isometric view of variousgraspable projections or other gripping means 3532, 3632, 3732, 3832extending from a proximal end of a lacrimal implant 3500, 3600, 3700,3800. The graspable or other projections 3532, 3632, 3732, 3832 can beused for various functions, including providing a structure to which auser can grasp onto during implant insertion or removal, inhibiting orpreventing the associated lacrimal implant from passing completelywithin a lacrimal punctum 212, 214 and associated canaliculus 208, 210(FIG. 2), or for providing tactile or visual feedback information to theuser, e.g., as to whether the implant is fully implanted.

In some examples, as shown in FIG. 35, the graspable projection 3532 caninclude two or more expandable arm members, which are sized to rest onan exterior of the lacrimal punctum. The arm members can be affixed toan implant body 3502, for example, via molding, adhesion or welding. Theexpandable arm members are capable of expanding so as to limitpenetration of the lacrimal implant 3500 through the lacrimal punctum212, 214 and into the associated canaliculus 208, 210. While two armmembers are shown, some include more than two arm members, such as fourarm members. The expandable arm members can assume an expanded profileseparation distance 3505 that corresponds to about twice a diameter ofthe implant body, such that proximal ends of the proximal expandable armmembers remain on the exterior of the punctum. The expandable armmembers can expand in many ways from the narrow profile configuration tothe expanded profile configuration, and can include at least one of acoil, a braid, a suture, a thermoset polymer, a thermoplastic, a heatactivated material, Nitinol, a shape memory material, a polymer,polypropylene, polyester, nylon, natural fibers, stainless steel,polymethylmethacrylate or polyimide. In some examples, the expandablearm members can be expanded manually, for example by a physician, afterthe lacrimal implant has been positioned in the canalicular lumen 208,210.

In some examples, as shown in FIG. 36, the graspable projection 3632 caninclude a loop of a filament embedded in the proximal end of thelacrimal implant 3600 to permit removal of the implant with proximaltension to the loop, for example with forceps. In some examples, theloop of filament assumes a shape similar to a purse handle that extendsfrom the lacrimal implant with a loop so as to facilitate removal of thelacrimal implant. The filament can comprise at least one of a heatactivated material, Nitinol, a shape memory material, a polymer,polypropylene, polyester, nylon, natural fibers, stainless steel,polymethylmethacrylate or polyimide. In some embodiments, the filamentmay comprise an absorbable thermo plastic polymer, for example at leastone of polylactic acid (PLA), poly glycolic acid (PGA) or polylacticco-glycolic acid (PLGA). A distal end of the filament can be embeddedin, molded to or other affixed to an implant body 3602 so as to securethe filament to the lacrimal implant.

In some examples, as shown in FIG. 37, the graspable projection 3732 caninclude at least one axially extending projection coupled with animplant body 3702, which is configured to bias an outer most portion ofthe lacrimal canaliculus 208, 210. Due to the natural constrictionagainst outward biasing of the canaliculus, the interplay between theaxially extending projections and the canaliculus inhibits overinsertion of an associated lacrimal implant 3700.

In some examples, as shown in FIG. 38, a longitudinal indentation,channel or other recess 3832 in an implant body 3802 can be used in lieuof a graspable projection to permit insertion or removal of a lacrimalimplant 3800. The indentation, channel or other recess 3832 may extendaxially along only a portion of an implant body a sufficient distance tofacilitate removal of an associated lacrimal implant. In furtherexamples, a lacrimal implant can include a filament molded into animplant body and extending proximally for removal of the implant fromthe punctum.

FIGS. 39A-39B illustrate examples of an isometric view of a drug insert322 and a removal facilitating filament 3999. In some examples, as shownin FIG. 39A, the filament 3999 can extend from the drug insert 322 andis molded therein for removal purposes. Among other things, the filament3999 can comprise a suture, a thermoset polymer, or a shape memoryalloy. In some examples, as shown in FIG. 39B, the filament 3999 extendsalong the drug insert 322 adjacent an implant body 3902 and is bonded toa distal end of the insert for removal purposes. Filament can be bondedto the distal end of the drug core insert with an adhesive, such ascyanoacrylate, acrylic, epoxy, urethane or a hot melt adhesive.

FIG. 40 is a block diagram illustrating an example of a method 4000 ofmanufacturing a lacrimal implant configured to be at least partiallyinsertable through a lacrimal punctum and into the associatedcanaliculus. At 4002, an implant body extending from a proximal end of afirst body portion to a distal end of a second body portion is formed.In some examples, various sizes of implant bodies are formed to fitvarious patient anatomies. In various examples, the proximal end isformed to define a longitudinal proximal axis and the distal end isformed to define a longitudinal distal axis. A formation of the implantbody can be configured such that, when implanted, the proximal axis andthe distal axis intersect at an angle of at least 45 degrees tolaterally bias at least a portion of the implant body against at least aportion of a lacrimal canaliculus located at or more distal to acanaliculus curvature.

In some examples, the second body portion is formed to include a dilatorgenerally narrowing from a location near a proximal end of the secondbody portion to the distal end of the second body portion. In someexamples, the dilator is formed by sloping an outer surface of thesecond portion of the implant body between about 1 degree and about 10degrees with respect to the longitudinal distal axis. In some examples,the outer surface of the second implant body portion is sloped to adilator tip of between about 0.2 millimeters and about 0.5 millimeters.

In some examples, the implant body is formed to include a graspable orother projection extending laterally from the proximal end of the firstbody portion. In certain examples, the projection is formed tosubstantially align with a lateral extension direction of the secondbody portion relative to the first body portion. In certain examples,the projection is formed such that, when implanted, it laterally extendsfrom the proximal end of the first body portion in a direction that isparallel to or away from an eye.

At 4004, a drug insert is disposed in at least one of the first bodyportion or the second body portion. In various examples, the drug insertis positioned such that an exposed drug insert surface sits adjacent atleast one of the proximal end or the distal end for providing asustained drug or other therapeutic agent release to an eye, nasalpassage or inner ear, for example. In certain examples, a first druginsert is disposed in the first body portion and a second drug insert isdisposed in the second body portion. In various examples, the one ormore drug inserts comprise drug cores including the drug or othertherapeutic agent.

At 4006, an outer surface portion of the implant body is coated with atleast one of a fluid swellable material, a lubricious coating or anantimicrobial coating. In various examples, the outer surface portion ofthe implant body is polished using a polishing process.

Sheath Body Examples:

In various ways, the sheath body can comprise appropriate shapes andmaterials to control migration of drug or other therapeutic agents froma drug insert. In some examples, the sheath body is configured to beconformable to an implant anatomy, such as an anatomy of a lacrimalpunctum or associated canaliculus. As discussed, in some examples, thesheath body at least partially covers or surrounds the drug insert andcan fit snugly against an outer surface of a matrix/agent mixture. Thesheath body can be made from a material that is substantiallyimpermeable to the drug or other therapeutic agent so that the rate ofmigration of the drug or agent is largely controlled by an exposedsurface area of the drug insert that is not covered by the sheath body.In many examples, migration of the agents through the sheath body can beabout one tenth of the migration of the agent through the exposedsurface of the drug insert, or less. Suitable sheath body materials caninclude, among others, polyimide, polyethylene terephthalate (PET). Thesheath body can have a thickness, as defined from the sheath surfaceadjacent the outer matrix/agent mixture surface to an opposing sheathsurface away from the outer surface, of about 0.00025 inches to about0.0015 inches. The total diameter of the sheath that extends across thedrug insert ranges from about 0.2 millimeters to about 1.2 millimeters.The drug insert can be formed by dip coating the matrix in the sheathbody. In some examples, the sheath body can comprise a tube into whichthe matrix/agent mixture is introduced. The sheath body can also be dipcoated around the matrix/agent mixture, for example dip coated around apre-formed matrix/agent core.

The sheath body can be provided with one or more additional featuressuch as to facilitate clinical use of the lacrimal implants discussedherein. For example, the sheath can receive a drug insert that isexchangeable in situ, while the implant body remains implanted in thepatient, or after its removal. In some examples, the sheath body can beprovided with one or more external protrusions that apply force to thesheath body when squeezed, which cause the matrix/agent mixture to beejected from the sheath body. A replacement drug insert can then bepositioned in the sheath body.

Therapeutic Agent Examples:

A therapeutic agent (or simply “agent”) can comprise, among otherthings, a drug made from one or any combination of the following ortheir equivalents, derivatives or analogs, including, anti-glaucomamedications, (e.g. adrenergic agonists, adrenergic antagonists (betablockers), carbonic anhydrase inhibitors (CAIS, systemic and topical),parasympathomimetics, prostaglandins and hypotensive lipids, andcombinations thereof), antimicrobial agent (e.g., antibiotic, antiviral,antiparacytic, antifungal, etc.), a corticosteroid or otheranti-inflammatory (e.g., an NSAID or other analgesic and pain managementcompounds), a decongestant (e.g., vasoconstrictor), an agent thatprevents of modifies an allergic response (e.g., an antihistamine,cytokine inhibitor, leucotriene inhibitor, IgE inhibitor,immunomodulator), a mast cell stabilizer, cycloplegic, mydriatic or thelike.

Example available agents include, but are not limited to, thrombininhibitors; antithrombogenic agents; thrombolytic agents; fibrinolyticagents; vasospasm inhibitors; vasodilators; antihypertensive agents;antimicrobial agents, such as antibiotics (such as tetracycline,chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin,cephalexin, oxytetracycline, chloramphenicol, rifampicin, ciprofloxacin,tobramycin, gentamycin, erythromycin, penicillin, sulfonamides,sulfadiazine, sulfacetamide, sulfamethizole, sulfisoxazole,nitrofurazone, sodium propionate), antifungals (such as amphotericin Band miconazole), and antivirals (such as idoxuridine trifluorothymidine,acyclovir, gancyclovir, interferon); inhibitors of surface glycoproteinreceptors; antiplatelet agents; antimitotics; microtubule inhibitors;anti-secretory agents; active inhibitors; remodeling inhibitors;antisense nucleotides; anti-metabolites; antiproliferatives (includingantiangiogenesis agents); anticancer chemotherapeutic agents;anti-inflammatories (such as hydrocortisone, hydrocortisone acetate,dexamethasone 21-phosphate, fluocinolone, medrysone, methylprednisolone,prednisolone 21-phosphate, prednisolone acetate, fluoromethalone,betamethasone, triamcinolone, triamcinolone acetonide); non steroidalanti-inflammatories (NSAIDs) (such as salicylate, indomethacin,ibuprofen, diclofenac, flurbiprofen, piroxicam indomethacin, ibuprofen,naxopren, piroxicam and nabumetone). Examples of such anti-inflammatorysteroids contemplated for use with the present lacrimal implants,include triamcinolone acetonide (generic name) and corticosteroids thatinclude, for example, triamcinolone, dexamethasone, fluocinolone,cortisone, prednisolone, flumetholone, and derivatives thereof);antiallergenics (such as sodium chromoglycate, antazoline,methapyriline, chlorpheniramine, cetrizine, pyrilamine,prophenpyridamine); anti proliferative agents (such as 1,3-cis retinoicacid, 5-fluorouracil, taxol, rapamycin, mitomycin C and cisplatin);decongestants (such as phenylephrine, naphazoline, tetrahydrazoline);miotics and anti-cholinesterase (such as pilocarpine, salicylate,carbachol, acetylcholine chloride, physostigmine, eserine, diisopropylfluorophosphate, phospholine iodine, demecarium bromide);antineoplastics (such as carmustine, cisplatin, fluorouracil3;immunological drugs (such as vaccines and immune stimulants); hormonalagents (such as estrogens,--estradiol, progestational, progesterone,insulin, calcitonin, parathyroid hormone, peptide and vasopressinhypothalamus releasing factor); immunosuppressive agents, growth hormoneantagonists, growth factors (such as epidermal growth factor, fibroblastgrowth factor, platelet derived growth factor, transforming growthfactor beta, somatotrapin, fibronectin); inhibitors of angiogenesis(such as angiostatin, anecortave acetate, thrombospondin, anti-VEGFantibody); dopamine agonists; radiotherapeutic agents; peptides;proteins; enzymes; extracellular matrix; components; ACE inhibitors;free radical scavengers; chelators; antioxidants; anti polymerases;photodynamic therapy agents; gene therapy agents; and other therapeuticagents such as prostaglandins, antiprostaglandins, prostaglandinprecursors, including antiglaucoma drugs including beta-blockers such asTimolol, betaxolol, levobunolol, atenolol, and prostaglandin analoguessuch as bimatoprost, travoprost, latanoprost etc; carbonic anhydraseinhibitors such as acetazolamide, dorzolamide, brinzolamide,methazolamide, dichlorphenamide, diamox; and neuroprotectants such aslubezole, nimodipine and related compounds; and parasympathomimetricssuch as pilocarpine, carbachol, physostigmine and the like.

Additional agents that can be used with the present lacrimal implantsinclude, but are not limited to, drugs that have been approved underSection 505 of the United States Federal Food, Drug, and Cosmetic Act orunder the Public Health Service Act, some of which can be found at theU.S. Food and Drug Administration (FDA) websitehttp://www.accessdata.fda.gov/scripts/cder/drugsatfda/index. The presentlacrimal implants can also be used with drugs listed in the Orange Book,either in paper or in electronic form, which can be found at the FDAOrange Book website (http://www.fda.gov/cder/ob/)), that has or recordsthe same date as, earlier date than, or later date than, the filing dateof this patent document. For example, these drugs can include, amongothers, dorzolamide, olopatadine, travoprost, bimatoprost, cyclosporin,brimonidine, moxifloxacin, tobramycin, brinzolamide, aciclovir timololmaleate, ketorolac tromethamine, prednisolone acetate, sodiumhyaluronate, nepafenac, bromfenac,diclofenac, flurbiprofen, suprofenac,binoxan, patanol, dexamethasone/tobramycin combination, moxifloxacin, oracyclovir.

Examples of diseases or disorders that can be treated with above-listedagents include, but are not limited to, glaucoma, pre- and post-surgicalocular treatments, dry eye, anti-eye allergy, anti-infective,post-surgical inflammation or pain, respiration-related disorders, suchas allergies, inner ear disorders, such as dizziness or migraines, orother systemic disorders, such as hypertension, cholesterol management,pulmonary disorders or immunological disorders. In some examples, thetherapeutic agent can include a lubricant or a surfactant, for example alubricant to treat dry eye. In other examples, the therapeutic agent caninclude an absorbent capable of absorbing tear from an eye.

Drug Insert Examples:

The drug insert can comprise one or more drugs or other therapeuticagents, and in some examples, one or more matrix materials to providesustained release of the drug or other agents. The one or more drugs orother therapeutic agents can migrate from an exposed surface of the druginsert to the target tissue (e.g., ciliary muscles of an eye) based, atleast in part, on a solubility of the drugs or agents in the matrix. Therate of migration of the drugs or agents from the exposed surface canalso be related to the concentration of drugs or agents dissolved in thematrix. In some examples, the concentration of drugs or agents dissolvedin the drug insert can be controlled to provide the desired release rateof the drugs or agents. In addition or in combination, the rate ofmigration of drugs or agents from the exposed surface can be related toone or more properties of the matrix in which the drugs or agentsdissolve, such as the properties of a silicone matrix formulation. Insome examples, the drugs or agents included in the drug insert caninclude liquid, solid, solid gel, solid crystalline, solid amorphous,solid particulate, or dissolved forms. In one such example, liquidLatanoprost droplets or solid Bimatoprost particles are dispersed in asilicone matrix.

The drug insert can comprise one or more biocompatible materials capableof providing a sustained release of the one or more drugs or agents.Although the drug insert is primarily discussed above with respect to anexample comprising a matrix including a substantially non-biodegradablesilicone matrix with dissolvable inclusions of the drugs or agentslocated therein, the drug insert can include other structures thatprovide sustained release of the drugs or agents, for example abiodegradable matrix, a porous drug insert, a liquid drug insert or asolid drug insert. A matrix that includes the drugs or agents can beformed from either biodegradable or non-biodegradable polymers. In someexamples, a non-biodegradable drug insert can include silicone,acrylates, polyethylenes, polyurethane, polyurethane, hydrogel,polyester (e.g., DACRON® from E. I. Du Pont de Nemours and Company,Wilmington, Del.), polypropylene, polytetrafluoroethylene (PTFE),expanded PTFE (ePTFE), polyether ether ketone (PEEK), nylon, extrudedcollagen, polymer foam, silicone rubber, polyethylene terephthalate,ultra high molecular weight polyethylene, polycarbonate urethane,polyurethane, polyimides, stainless steel, nickel-titanium alloy (e.g.,Nitinol), titanium, stainless steel, cobalt-chrome alloy (e.g., ELGILOY®from Elgin Specialty Metals, Elgin, Ill.; CONICHROME® from CarpenterMetals Corp., Wyomissing, Pa.). In some examples, a biodegradable druginsert can comprise one or more biodegradable polymers, such as protein,hydrogel, polyglycolic acid (PGA), polylactic acid (PLA), poly(L-lacticacid) (PLLA), poly(L-glycolic acid) (PLGA), polyglycolide,poly-L-lactide, poly-D-lactide, poly(amino acids), polydioxanone,polycaprolactone, polygluconate, polylactic acid-polyethylene oxidecopolymers, modified cellulose, collagen, polyorthoesters,polyhydroxybutyrate, polyanhydride, polyphosphoester, poly(alpha-hydroxyacid) and combinations thereof. In some examples, the drug insert cancomprise a hydrogel polymer.

Closing Notes:

Among other things, lacrimal implants and related methods providingsecure retention within a lacrimal punctum and canaliculus of an eye arediscussed herein. The lacrimal implants can comprise an implant bodyconfigured for at least partial insertion through the lacrimal punctumand into the canaliculus. The implant body can include first and secondportions, and can extend from a proximal end of the first portiondefining a longitudinal proximal axis to a distal end of the secondportion defining a longitudinal distal axis. The implant body can beconfigured such that, when implanted using an integral dilator, an atleast 45 degree angled intersection exists between the proximal axis andthe distal axis. In this way, at least a portion of the implant body canbe biased against at least a portion of the lacrimal canaliculus locatedat or more distal to a canalicular curvature, thereby retaining animplanted position of the lacrimal implant using anatomical structures.In various examples, the lacrimal implant can further comprise a druginsert disposed in at least one of the first portion or the secondportion of the implant body to provide a sustained release of a drug orother therapeutic agent to an eye, nasal passage, or inner ear system,for instance.

Advantageously, in some examples, the present lacrimal implants cansuccessfully block the flow of tears or provide sustained delivery of adrug or other therapeutic agent to an eye, nasal passage, or inner earfor varying periods of time, such as from days to months to years. Inaddition, by including first and second implant body cavities, a dualdrug or other agent releasing profile can be possible. For instance, twoseparate drugs can be released from two different implant locations.Further, the canalicular curve retaining configuration of the presentimplant body can reduce over-stretching of the lacrimal punctum andcanaliculus and inadvertent fall out of implants. Even further, it isbelieve the present lacrimal implants can be implemented so as toprovide a one-size-fits-all (or many) regime, as an expandable coatingor other expandable retention member can be applied to the implant body,such as an outer surface portion of the implant body, to fit in hollowtissue structures of varying sizes. The present lacrimal implant mayalso be better tolerated by a patient due to, for example, anorientation of a graspable or other projection located at the proximalend of the implant body.

The above Detailed Description includes references to the accompanyingdrawings, which form a part of the Detailed Description. The drawingsshow, by way of illustration, specific embodiments in which theinvention can be practiced. These embodiments are also referred toherein as “examples.” All publications, patents, and patent documentsreferred to in this document are incorporated by reference herein intheir entirety, as though individually incorporated by reference. In theevent of inconsistent usages between this document and those documentsso incorporated by reference, the usage in the incorporated reference(s)should be considered supplementary to that of this document; forirreconcilable Inconsistencies, the usage in this document controls.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one, independent of any otherinstances or usages of “at least one” or “one or more.” In thisdocument, the term “or” is used to refer to a nonexclusive or, such that“A or B” includes “A but not B,” “B but not A,” and “A and B,” unlessotherwise indicated. In this document, the term “about” is used to referto an amount that is approximately, nearly, almost, or in the vicinityof being equal to a stated amount.

In this document, the term “proximal” refers to a location relativelycloser to a hand of a physician implanting a lacrimal implant into apatient, and the term “distal” refers to a location relatively furtherfrom the hand of the physician, particularly during the implanting ofthe implant into the patient.

In this document, the term “hydrogel” is used to refer to an absorbingor otherwise retaining material (e.g., adsorbing material), such assuper-absorbent polymers, hydrocolloids, and water-absorbent hydrophilicpolymers, for example. In some examples, the term “hydrogel” refers tosuper-absorbent polymer particles in a “dry” state, more specifically,particles containing from no water up to an amount of water less thanthe weight of the particles, such as less than about 5%, by weight,water. In some examples, the term “hydrogel” refers to a super-absorbentpolymer in the “dry” state when the hydrogel is not expandable and alsorefers to its hydrated or expanded state, more specifically, hydrogelsthat have absorbed at least their weight in water, such as several timestheir weight in water. As the hydrogel material absorbs fluid, its sizecan increase (swell) and its shape can change to bias against at least aportion of a lacrimal canaliculus ampulla or lacrimal canaliculus wall,for example.

In the appended claims, the terms “including” and “in which” are used asthe plain-English equivalents of the respective terms “comprising” and“wherein.” Also, in the following claims, the terms “including” and“comprising” are open-ended, that is, a system, assembly, device,article, or process that includes elements in addition to those listedafter such a term in a claim are still deemed to fall within the scopeof that claim. Moreover, in the following claims, the terms “first,”“second,” and “third,” etc. are used merely as labels, and are notintended to impose numerical requirements on their objects.

The above description is intended to be illustrative, and notrestrictive. For example, the above-described examples (or one or morefeatures thereof) can be used in combination with each other. Otherembodiments can be used, such as by one of ordinary skill in the artupon reviewing the above description. Also, in the above DetailedDescription, various features can be grouped together to streamline thedisclosure. This should not be interpreted as intending that anunclaimed disclosed feature is essential to any claim. Rather, inventivesubject matter can lie in less than all features of a particulardisclosed embodiment. Thus, the following claims are hereby incorporatedinto the Detailed Description, with each claim standing on its own as aseparate embodiment. The scope of the invention should be determinedwith reference to the appended claims, along with the full scope ofequivalents to which such claims are entitled.

The Abstract is provided to comply with 37 C.F.R. §1.72(b), to allow thereader to quickly ascertain the nature of the technical disclosure. Itis submitted with the understanding that it will not be used tointerpret or limit the scope or meaning of the claims.

What is claimed is:
 1. A method of providing a sustained drug release toan eye using a lacrimal implant comprising at least one drug insert, themethod comprising: implanting the lacrimal implant in at least onelacrimal canaliculus, the lacrimal implant comprising; an implant body,comprising a first and second portions, the implant body non-linearlyextending from a proximal end portion positionable within a verticalsection of the lacrimal canaliculus to a distal end portion positionablewithin a horizontal section of the lacrimal canaliculus and having anintermediate portion therebetween, the proximal end of the first portiondefining a longitudinal proximal axis and the distal end of the secondportion defining a longitudinal distal axis, the first portion includinga cavity; a drug insert disposed in the cavity, the drug insertincluding a matrix, a therapeutic agent dissolved or dispersed in thematrix, and an impermeable sheath body disposed over at least a portionof the matrix to define at least one insert exposed surface located ator near the proximal end of the first portion implant body; theintermediate portion partially extending in a first direction toward theproximal end portion, partially extending in a second direction towardthe distal end portion, and partially extending in a third directionalong the longitudinal distal axis, configured to bias against a portionof a lacrimal canaliculus ampulla wherein the third direction isperpendicular to the first direction of the intermediate portion, suchthat, when implanted in the lacrimal canaliculus, the implant bodydirectionally biases laterally against at least a portion of thelacrimal canaliculus located at or more distal to a canalicularcurvature; wherein the drug insert is configured to provide a sustainedrelease of the therapeutic agent; and delivering the sustained releasetherapeutic agent over an extended period of at least one day to theeye, whereby a sustained drug release is provided to the eye.
 2. Themethod of claim 1, wherein the therapeutic agent is selected from thegroup consisting of thrombin inhibitors; antithrombogenic agents;thrombolytic agents; fibrinolytic agents; vasospasm inhibitors;vasodilators; antihypertensive agents; antimicrobial agents; antibioticagents; antifungal agents; antiviral agents; inhibitors of surfaceglycoprotein receptors; antiplatelet agents; antimitotics; microtubuleinhibitors; anti-secretory agents; active inhibitors; remodelinginhibitors; antisense nucleotides; anti-metabolites; antiproliferatives;anticancer chemotherapeutic agents; anti-inflammatories; non steroidalanti-inflammatories (NSAIDs); prostaglandins, prostaglandin analogues,antiprostaglandins, prostaglandin precursors, acetazolamide,dorzolamide, brinzolamide, methazolamide, dichlorphenamide, diamox;lubezole, nimodipine, pilocarpine, carbachol, physostigmine andcombinations thereof.
 3. The method of claim 1, wherein the therapeuticagent is a glaucoma drug selected from Timolol, betaxolol, levobunolol,atenolol, bimatoprost, travoprost, and latanoprost.
 4. The method ofclaim 1, wherein the sustained drug release provided to the eye treatsat least one of glaucoma, pre- and post-surgical ocular treatments, dryeye, anti-eye allergy, anti-infective, or post-surgical inflammation orpain.
 5. The method of claim 1, wherein the longitudinal length of thelacrimal implant body positionable within the vertical section of thelacrimal canaliculus is less than four times a longitudinal length ofthe implant-body positionable within the horizontal section of thelacrimal canaliculus.
 6. The method of claim 1, wherein the firstdirection extension of the intermediate portion of the lacrimal implantis at an angle between 45 degrees and 135 degrees relative to the seconddirection extension of the intermediate portion.
 7. The method of claim1, wherein the second direction extension of the lacrimal implantincludes a longitudinal dilator having a generally convex shape relativeto the first direction extension.
 8. The method of claim 1, wherein thesecond direction extension of the lacrimal implant includes alongitudinal dilator having an axis substantially perpendicular to anaxis of the first direction extension.
 9. The method of claim 1, whereinat least one of the proximal end portion or the distal end portion ofthe lacrimal implant comprises at least one intermediately-disposedannular, semi-annular, column-like, or barrel-like projection, theintermediately-disposed projection having a cross-sectional size greaterthan an adjacent implant body portion.
 10. The method of claim 1,wherein the lacrimal implant comprises a fluid swellable materialdisposed on an outer surface portion of the implant body, the fluidswellable material configured to expand an outer surface diameterportion of the implant body-when implanted.
 11. The method of claim 1,wherein the lacrimal implant further comprises a second drug insertdisposed in the distal end portion.
 12. The method of claim 1, whereinthe lacrimal implant comprises a first drug insert and a second druginsert, wherein the first drug insert comprises a therapeutic agentconfigured to treat an eye disorder; and the second drug insert isdisposed in a second cavity in the distal end portion, wherein thesecond drug insert comprises a therapeutic agent configured to bereceived by a nasal passage.
 13. The method of claim 1, wherein thesecond portion of the lacrimal implant includes an integral dilator, theintegral dilator narrowing from a location near a proximal end of thesecond portion to the distal end of the second portion to facilitateimplantation of the implant body into the lacrimal canaliculus.
 14. Themethod of claim 13, wherein a diameter of an integral dilator tip isbetween about 0.2 millimeters and about 0.5 millimeters.
 15. The methodof claim 13, wherein an outer surface slope of the integral dilator, asmeasured from the location near the proximal end of the second portionto the distal end of the second portion, is between about 1 degree andabout 10 degrees with respect to the distal axis.
 16. The method ofclaim 1, wherein the matrix comprises silicone, acrylates,polyethylenes, polyurethane, polyurethane, hydrogel, polyester,polypropylene, polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE),polyether ether ketone (PEEK), nylon, extruded collagen, polymer foam,silicone rubber, polyethylene terephthalate, ultra high molecular weightpolyethylene, polycarbonate urethane, polyurethane, polyimides,stainless steel, nickel-titanium alloy, titanium, stainless steel,cobalt-chrome alloy, protein, polyglycolic acid (PGA), polylactic acid(PLA), poly(L-lactic acid) (PLLA), poly(L-glycolic acid) (PLGA),polyglycolide, poly-L-lactide, poly-D-lactide, poly(amino acids),polydioxanone, polycaprolactone, polygluconate, polylacticacid-polyethylene oxide copolymers, modified cellulose, collagen,polyorthoesters, polyhydroxybutyrate, polyanhydride, polyphosphoester,poly(alpha-hydroxy acid) or combinations thereof.
 17. The method ofclaim 1, wherein the matrix comprises silicone or polyurethane.
 18. Amethod of treating an ocular disorder by providing a sustained drugrelease to an eye using a lacrimal implant comprising at least one druginsert, the method comprising: implanting the lacrimal implant in alacrimal canaliculus, wherein the lacrimal implant comprises; an implantbody, comprising a first and second portions, the implant bodynon-linearly extending from a proximal end portion positionable within avertical section of the lacrimal canaliculus to a distal end portionpositionable within a horizontal section of the lacrimal canaliculus andhaving an intermediate portion therebetween, the proximal end of thefirst portion defining a longitudinal proximal axis and the distal endof the second portion defining a longitudinal distal axis, the firstportion including a cavity; a drug insert disposed in the cavity, thedrug insert including a matrix, a therapeutic agent dissolved ordispersed in the matrix, and an impermeable sheath body disposed over atleast a portion of the matrix to define at least one insert exposedsurface located at or near the proximal end of the first portion implantbody; the intermediate portion partially extending in a first directiontoward the proximal end portion, partially extending in a seconddirection toward the distal end portion, and partially extending in athird direction along the longitudinal distal axis, configured to biasagainst a portion of a lacrimal canaliculus ampulla wherein the thirddirection is perpendicular to the first direction of the intermediateportion, such that, when implanted in the lacrimal canaliculus, theimplant body directionally biases laterally against at least a portionof the lacrimal canaliculus located at or more distal to a canalicularcurvature; wherein the drug insert is configured to provide a sustainedrelease of the therapeutic agent; and delivering the sustained releasetherapeutic agent over an extended period of at least one day to theeye, whereby the ocular disorder is treated.
 19. The method of claim 18,wherein the therapeutic agent is selected from Timolol, betaxolol,levobunolol, atenolol, bimatoprost, travoprost, latanoprost,antimicrobial agents; antibiotic agents; antifungal agents; antiviralagents; anti-inflammatories; or non steroidal anti-inflammatories(NSAIDs).
 20. The method of claim 19, wherein the ocular disorder is atleast one of glaucoma, dry eye, anti-eye allergy, ocular infection, orpost-surgical inflammation or pain.
 21. The method of claim 18, whereinthe matrix comprises silicone, acrylates, polyethylenes, polyurethane,polyurethane, hydrogel, polyester, polypropylene,polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), polyether etherketone (PEEK), nylon, extruded collagen, polymer foam, silicone rubber,polyethylene terephthalate, ultra high molecular weight polyethylene,polycarbonate urethane, polyurethane, polyimides, stainless steel,nickel-titanium alloy, titanium, stainless steel, cobalt-chrome alloy,protein, polyglycolic acid (PGA), polylactic acid (PLA), poly(L-lacticacid) (PLLA), poly(L-glycolic acid) (PLGA), polyglycolide,poly-L-lactide, poly-D-lactide, poly(amino acids), polydioxanone,polycaprolactone, polygluconate, polylactic acid-polyethylene oxidecopolymers, modified cellulose, collagen, polyorthoesters,polyhydroxybutyrate, polyanhydride, polyphosphoester, poly(alpha-hydroxyacid) or combinations thereof.
 22. The method of claim 18, wherein thematrix comprises silicone or polyurethane.
 23. A method of treatingocular, respiratory, inner ear, pulmonary, or inflammatory disorderusing a lacrimal implant comprising at least one drug insert, the methodcomprising: implanting the lacrimal implant in a lacrimal canaliculus,wherein the lacrimal implant comprises; an implant body, comprising afirst and second portions, the implant body non-linearly extending froma proximal end portion positionable within a vertical section of alacrimal canaliculus to a distal end portion positionable within ahorizontal section of the lacrimal canaliculus and having anintermediate portion therebetween, the proximal end of the first portiondefining a longitudinal proximal axis and the distal end of the secondportion defining a longitudinal distal axis, the first and/or secondportion including a cavity; a drug insert disposed in the cavity, thedrug insert including a matrix, a therapeutic agent dissolved ordispersed in the matrix, and an impermeable sheath body disposed over atleast a portion of the matrix to define at least one insert exposedsurface located at or near the proximal end of the first portion or thedistal end of the second portion; the intermediate portion partiallyextending in a first direction toward the proximal end portion,partially extending in a second direction toward the distal end portion,and partially extending in a third direction along the longitudinaldistal axis, configured to bias against a portion of a lacrimalcanaliculus ampulla wherein the third direction is perpendicular to thefirst direction of the intermediate portion, such that, when implantedin the lacrimal canaliculus, the implant body directionally biaseslaterally against at least a portion of the lacrimal canaliculus locatedat or more distal to a canalicular curvature; wherein the drug insert isconfigured to provide a sustained release of the therapeutic agent; anddelivering the therapeutic agent over an extended period of at least oneday to an eye, nasal passage or inner ear whereby at least one of theocular, respiratory, inner ear or inflammatory disorders is treated. 24.The method of claim 23, wherein the matrix comprises silicone orpolyurethane.
 25. The method of claim 24, wherein the lacrimal implantcomprises a first drug insert and a second drug insert, wherein thefirst drug insert comprises a therapeutic agent configured to treat aneye disorder; and the second drug insert is disposed in a second cavityin the distal end portion, wherein the second drug insert comprises atherapeutic agent configured to be received by a nasal passage.
 26. Themethod of claim 25, wherein the therapeutic agent is selected from thegroup consisting of thrombin inhibitors; antithrombogenic agents;thrombolytic agents; fibrinolytic agents; vasospasm inhibitors;vasodilators; antihypertensive agents; antimicrobial agents; antibioticagents; antifungal agents; antiviral agents; inhibitors of surfaceglycoprotein receptors; antiplatelet agents; antimitotics; microtubuleinhibitors; anti-secretory agents; active inhibitors; remodelinginhibitors; antisense nucleotides; anti-metabolites; antiproliferatives;anticancer chemotherapeutic agents; anti-inflammatories; non steroidalanti-inflammatories (NSAIDs); prostaglandins, prostaglandin analogues,antiprostaglandins, prostaglandin precursors, acetazolamide,dorzolamide, brinzolamide, methazolamide, dichlorphenamide, diamox;lubezole, nimodipine, pilocarpine, carbachol, physostigmine andcombinations thereof.
 27. The method of claim 23, wherein the matrixcomprises silicone, acrylates, polyethylenes, polyurethane,polyurethane, hydrogel, polyester, polypropylene,polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), polyether etherketone (PEEK), nylon, extruded collagen, polymer foam, silicone rubber,polyethylene terephthalate, ultra high molecular weight polyethylene,polycarbonate urethane, polyurethane, polyimides, stainless steel,nickel-titanium alloy, titanium, stainless steel, cobalt-chrome alloy,protein, polyglycolic acid (PGA), polylactic acid (PLA), poly(L-lacticacid) (PLLA), poly(L-glycolic acid) (PLGA), polyglycolide,poly-L-lactide, poly-D-lactide, poly(amino acids), polydioxanone,polycaprolactone, polygluconate, polylactic acid-polyethylene oxidecopolymers, modified cellulose, collagen, polyorthoesters,polyhydroxybutyrate, polyanhydride, polyphosphoester, poly(alpha-hydroxyacid) or combinations thereof.